Perinatal Depression, Perinatal Anxiety
Conditions
Keywords
Cognitive Behavioral Couple Therapy (with or without Zikr), Pharmacology Intervention, Their combination
Brief summary
The hypotheses of the study are * There will be differences in perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being in couples at Pre- and Post-Test levels during the perinatal period in couples. * There will be differences with psychopharmacological intervention on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between the experimental and wait list-placebo control groups. * There will be differences in CBCT (condition: without Zikr) on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between the experimental and wait list control group. * There will be differences in CBCT (condition: with Zikr) on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between the experimental and wait list-placebo control groups. * There will be differences for combined psychopharmacology, and CBT (conditions: with Zikr, without Zikr ) dimensions on total scores of perceived perinatal distress, dyadic coping strategies, social support, domains of quality of life, and well-being between experimental and wait list-placebo control group.
Detailed description
The research questions of the study are • How effective will psychopharmacological treatment, CBCT (with or without Zikr) and combined medicine-CBCT (with or without Zikr) interventions be in reducing symptoms of distress among couples during the perinatal period through a randomized clinical trial? * Will dyadic coping strategies, social support, domains of quality of life, and well-being be improved in couples at the post-test level compared to the pre-test level by therapeutic intervention through a randomized clinical trial? * What will be the effect size of post-test intervention? Procedures and Protocol The investigator will ask willing participants (screened for high risk) to select one of their preferred treatment modes out of the following 1. Medications (antidepressants and/or anxiolytics). 2. Cognitive Behavioural Therapy without Zikr. 3. Cognitive Behavioural Therapy with Zikr. 4. Combination of medications and cognitive behavioral therapy. 5. Combination of medications, cognitive behavioral therapy, and Zikr. A list of willing participants will be prepared. Each participant will have one in five chances of getting the preferred treatment mode after study is over. There will be two groups (experimental and control). To put people into one of the two groups, the investigator will select by randomization via online calculator random number generation. Participants will not know to which group they actually belong. This information will be recorded in the investigator's files, but the research assistant will not look at these files until after the research is finished. This is the best way the investigators have to testing without being influenced by what they think or hope might happen. Thus, the participants and the research assistant will be double blinded in the trial. The investigator and research assistant will then compare which of the two has the best results. The healthcare professionals (consultant gynecologists and investigator's research assistant) will be looking after the participants very carefully during the study. If there are anything participants are concerned about or that is bothering them about the research they will talk to the researcher, research assistant, gynaecologist or staff. A placebo or inactive medicine looks like real medicine but it is not. It is a dummy or pretend medicine. It has no effect on a person because it has no real medicine in it. The investigator wants to know whether medicine is good, therefore some people will be given the medicine and others will be given the pretend or a dummy medicine. For the research to be good, it is important that participants do not know whether they have been given real medicine or pretend or dummy medicine. This is one of the best ways the investigator have for knowing what the medicine that are being tested really does. But the participants given a placebo or no intervention will be informed at the end of the study and will be given treatment with medication as they are wait-list control. Moreover, the participants in the intervention group will receive their preferred treatment after the completion of the study. Participants will receive psychopharmacological treatment according to the National Institute for Health and Care Excellence (NICE) guidelines. Description of the Process During the research, a couple has to make ten visits to attend ten sessions in the hospital. • In the first visit, rapport will be built and pre-test assessment will be done in the following two approaches Quantitative Approach • Indigenously developed Parental Perinatal Distress Scale (PPDS). * Multidimensional Scale for Perceived Social Support (MSPSS). * Dyadic Coping Inventory (DCI). * Flourishing Scale (FS). * World Health Organization's Quality of Life Brief (WOLQOL-BREF) Qualitative Approach • In a qualitative approach, the semi-structured interviews will be conducted to explore the present stressors and expectations, and perceptions about the effectivity of treatments for perinatal distress among couples. Group 1 will be given medications or placebo for two weeks and/or for four to five weeks maximum (as per requirement) by the consultant gynaecologist. They have to visit after two weeks for post-test assessment. After treatment, the medicine will be tapered off to stop the intake. As explained before, neither participant will know whether they have received the medicine or the placebo. But in the end placebo participants will be debriefed and will be continued with real medication. Group 2, Group 3, Group 4 and Group 5 will continue the following 10 sessions (two sessions, each one hour per week) of CBCT with the investigator. • In the second session, participants will be psycho-educated for perinatal period distress, couples' physical and mental health and impact on the fetus-infant, the prevalence of depression and anxiety, and the significance of identification. Progressive muscle relaxation exercises will be carried out along with deep breathing. Feedback on the session will be taken. • In the third session, participants will be psycho-educated on the theoretical model of cognitive-behavioral couple therapy with some historical highlights and empirical standing. A thought log will be given for homework. Feedback for deep breathing and progressive muscle relaxation will be carried out. • In the fourth, fifth, sixth, seventh, eighth, and ninth session, feedback will be taken on homework and session. Various techniques of Cognitive Behavioural Couple Therapy will be applied based on the nature and contents of identified precipitating, perpetuating, and present stressors. In addition, relevant techniques will be incorporated from other modalities with eclecticism. Tasbeeh in Zikr will be given to group 3 and group 5 who opted for it in the screening process. • On the tenth visit, feedback on the session and homework will be taken. post-test assessment will be done in the following two approaches Group 6 will be exposed to one of the two conditions. 50% of couples will get a placebo and 50% will receive routine treatment care with no intervention. However, after the completion of the research, intervention groups and waitlist group (control) will be briefed and will be delivered with an intervention mode of treatment of their choice as selected earlier. Posttest assessment will be carried out by the following instruments Quantitative Approach • Indigenously developed Parental Perinatal Distress Scale (PPDS). • Multidimensional Scale for Perceived Social Support (MSPSS). • Dyadic Coping Inventory (DCI). • Flourishing Scale (FS). * World Health Organization's Quality of Life Brief (WOLQOL-BREF) Qualitative Approach * In a qualitative approach, the semi-structured interview will be conducted to explore the conception about the perinatal distress and perceptions about effectivity of treatments for perinatal distress among couples. Duration The research takes place from 15th August, 2023 to 30th September, 2023. Screening (for Major Depressive Disorder, Generalized Anxiety Disorder) with PPDS will be carried out on the couples who visit the gynecological ward of the hospital in August. After screening and signed informed consent, it will be necessary for participants to come to the clinic/hospital for 10 days in total, for one hour session each day in end of August and whole month of September (two sessions per week, each for one hour). The investigator and the research assistant would like to meet with participants twice in the upcoming month after the participant's last session visit for a final check-up in follow-ups.
Interventions
DRUGPsychopharmacological Intervention
Escitalopram 5-10 mg in antenatal period; Sertraline 12.5-25 mg in postnatal period) and/or Benzodiazepine (Alprazolam, 0.25-0.50 mg).
BEHAVIORALCognitive Behavioral Couple Therapy
CBCT intervention from a trained psychologist in CBT.
OTHERCombination of Psychopharmacological Intervention and CBCT
Medication will be prescribed by a consultant gynecologist and CBCT (conditions: with or without Zikr) will be provided by a trained psychologist.
OTHERPlacebo and No Intervention
Control waitlist group will be provided with either a placebo by a consultant gynaecologist or no intervention by a trained psychologist
Sponsors
Sameera Shafiq
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SCREENING
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Participants will be randomly assigned to any of the above six arms by random number generation via online calculator.net. The outcome assessor (research assistant) will not be provided with information regarding the allocation of the participants to each group. Hence, the research assistant and participants will be blind to getting the questionnaires filled.
Intervention model description
The first arm receives psychopharmacological medication. The second arm received CBCT (without Zikr). The third arm received CBCT (with Zikr). The fourth receives a combination of psychopharmacological medication and CBCT without Zikr The fifth arm receives a combination of psychopharmacological medication, CBCT, and with Zikr. The sixth control group receives either a placebo or no CBCT intervention
Eligibility
Sex/Gender
ALL
Age
19 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* The fourth month of pregnancy till the seventh month of the antenatal period. * One week after delivery/birth till one year of a child in the postnatal period. * Screened by PPDS as high-risk couples (for the level of severe symptomology) for Major Depressive Disorder (cut-off score 29 to 42) and/or Generalized Anxiety Disorder (cut-off score 17 to 24), and their Comorbidity. * Dose requirements in any one of the antidepressant and/or anxiolytic, such as escitalopram (5-10 mg), sertraline (12.5-25 mg), and/or alprazolam (0.25-0.50 mg) per day. * Wives accompanied by their husbands. * Willingness to participate as a couple in the study. * No physical disorder is present and/or no medication use. * No psychiatric disorder history or presence * No psychotropic medication use (presence or history) * No disability is present.
Exclusion criteria
* Unwilling couples to participate in the study. * Wife and/or couple is in an emergency. * Wife and/or couple has unstable mental health. * Wife accompanied by close relatives other than a spouse. * Wife in the first week of delivery. * Dose requirements in any one of the antidepressant and/or anxiolytic, such as escitalopram (above10 mg), sertraline (above 25 mg), and/or alprazolam (above 0.50 mg) per day. * Couples screened with depressive disorder and/or anxiety disorder having psychotic features. * Couples screened with depressive disorder and/or anxiety disorder having suicidal ideation. * Couples screened with depressive disorder and/or anxiety disorder having mania/hypomanic features. * Couples having diabetes. * Couples having cardiovascular disorders. * Presence or history of any physical or psychiatric disorder and/or use of medications * Any intellectual, visual, or hearing disability present in either spouse of a couple.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion. | The Multidimensional Scale for Perceived Social Support comprised 12 items. There are 1 to 7 scoring categories. The sum of score for 12 items range from 12 (minimum) to 84 (maximum). The high score indicates better social support for perinatal couples. In the present study, data mean and standard deviation specifies absolute values in post-test assessment. |
| The Sum of Scores on Flourishing Scale (FS) | After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion. | The Flourishing Scale comprised 8 items with 1 to 7 scoring categories. Sum of scores range from 8 (minimum) to 56 (maximum) for eight items. The high score indicates better well-being in perinatal couples. In the present study, data mean and standard deviation specifies absolute values in pre-test and post-test assessment. |
| The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion. | World Health Organization Quality of Life Bref (WHOQOL-BREF) comprised 26 items with 1 to 5 scoring categories. Item 1 and item 2 were not included in the scoring domains because these were evaluative items. The remaining 24 items are classified in four subscales (physical, psychological, social, and environmental) of quality of life. Sum of scores for physical aspect (7 items) of life ranged from 7 (minimum) to 35 (maximum); 6(minimum) to 30 (maximum) for psychological subscale (6 items); 3 (minimum) to 20 (maximum) for social subscale(3 items); and 8 (minimum) to 40 (maximum) for environmental subscale (8 items) of life. The high score indicates a better quality of life in that particular subscale domain in perinatal couples. In the present study, data mean and standard deviation specifies absolute values in pre-test and post-test assessment. |
| The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion. | The Generalized Anxiety Disorder Subscale and Major Depressive Disorder Subscale comprised 8 and 14 items respectively in Parental Perinatal Distress Scale. The response categories range from 0 to 3 scale. The total number of items in both subscales is 22. The summed scores obtained on 22 items range from 0 (minimum) to 66 (maximum). The high total score indicates worse symptoms of perinatal distress in the couples. In the present study, data mean and standard deviation specify absolute value at a pre-test and post-test assessment. |
| The Sum of Scores on Dyadic Coping Inventory (DCI) | After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion. | Dyadic Coping Inventory comprised 37 items with 1 to 5 scoring categories. However, items 36 and 37 were not included in the scoring as these were evaluative items. The sum of scores for the remaining 35 items range from 35 (minimum) to 175 (maximum). The high score indicates better-than-average levels of coping skills in perinatal couples. In the present study, data mean and standard deviation specifies absolute values in post-test assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Blood Concentration (Either ng/ml or mg/L) Levels for Escitalopram and Sertraline | After recruitment, screening, randomization, and allocation, changes in blood concentration levels for Escitalopram and Sertraline as assessed on week 12 (follow-up) through the study period (two and half months). | Gynaecologist prescribed 5 mg/day escitalopram antenatally or 12.5 mg/day sertraline postnatally. Assessment of blood concentration level via High Performance Liquid Chromatography was conditioned on consent of the participants. The overall number of participants analyzed in Secondary Outcome Period Participants (1st Oct to 28 Oct) represent the total number of participants from the Primary Outcome Period, for each Arm/Group. The data were not collected and the outcome cannot be reported for arms without psychopharmacological intervention including 0 participants. The participants withdrew from HPLC to avoid expansive biomedical tests, adhering to Pakistani cultural norm. The toxicity levels is not reported in the blood of the couples because 5 mg/day escitalopram (Eichentopf et al; Bellantuono et al) or 12.5 mg/day sertraline (Almurjan et al ; Heinonen et al) and is considered safe dose range with no sign of toxicity in blood concentration levels and no presence of adverse events. |
| Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | After recruitment, screening, randomization, and allocation, number of participants with treatment-related adverse events as assessed by CTCAE v4.0 on week 11 and week 12 (follow-ups) through the study period (two and half months). | Side effects of escitalopram and sertraline (5 mg/day, and 12.5 mg/day respectively) classified as Grade 1 level in CTCAE v4.0 as these settle down within two to three weeks of medication. A checklist assessed presence or absence of adverse events among participants in psychopharmacological intervention arm, combined intervention without zikr arm, and combined intervention with zikr arm qualitatively. The overall number of participants analyzed in Secondary Outcome Period Participants (1st Oct to 28 Oct) represent the total number of participants for whom an Outcome Measure was measured and analyzed from the Primary Outcome Period Participants, for each Arm/Group. The data were not collected and the outcome cannot be reported for arms without psychopharmacological intervention including 0 participants analyzed because medication was not administered. |
Countries
Pakistan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Psychopharmacological Intervention Escitalopram (5 mg) is prescribed by a gynecologist to high-risk couples in the antenatal period and to husbands in the postnatal period.
Sertraline (12.5 mg) is prescribed by a gynecologist to women in postnatal period.
Alprazolam (0.25 mg) is prescribed by a gynecologist to couples in antenatal and postnatal period. | 14 |
| CBCT Without Zikr Intervention 10 sessions each of 0ne hour, twice a week were carried out. | 16 |
| CBCT With Zikr Intervention 10 sessions each of 0ne hour, twice a week were carried out.
Zikr (Ya Salam-The Peace Giver, Ya Rehman-The Merciful) was given for recitation. | 16 |
| Combined Intervention Without Zikr Escitalopram (5 mg) is prescribed by a gynecologist to high-risk couples in the antenatal period and to husbands in the postnatal period.
Sertraline (12.5 mg) is prescribed by a gynecologist to women in postnatal period.
Alprazolam (0.25 mg) is prescribed by a gynecologist to couples in antenatal and postnatal period.
10 sessions each of 0ne hour, twice a week were carried out. | 8 |
| Combined Intervention With Zikr Escitalopram (5 mg) is prescribed by a gynecologist to high-risk couples in the antenatal period and to husbands in the postnatal period.
Sertraline (12.5 mg) is prescribed by a gynecologist to women in postnatal period.
Alprazolam (0.25 mg) is prescribed by a gynecologist to couples in antenatal and postnatal period.
10 sessions each of 0ne hour, twice a week were carried out.
Zikr (Ya Salam-The Peace Giver, Ya Rehman-The Merciful) were given for recitation. | 10 |
| Placebo Comparator Sugar Pill was prescribed by a gynecologist. | 6 |
| No Intervention Routine medical/gynecological checkups were carried out. | 8 |
| Total | 78 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| 15 August 2023 to 30 September 2023 | Withdrawal by Subject | 2 | 0 | 0 | 8 | 6 | 2 | 0 |
| 1 October 2023 to 28 October 2023) | Withdrawal by Subject | 14 | 0 | 0 | 8 | 10 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Psychopharmacological Intervention | CBCT Without Zikr Intervention | CBCT With Zikr Intervention | Combined Intervention Without Zikr | Combined Intervention With Zikr | Placebo Comparator | No Intervention |
|---|---|---|---|---|---|---|---|---|
| Absolute Value of Score for Psychological Subscale of World Health Organization Quality of Life Bref | 8.65 units on a scale STANDARD_DEVIATION 1.07 | 8.500 units on a scale STANDARD_DEVIATION 1.09 | 7.93 units on a scale STANDARD_DEVIATION 1.28 | 8.93 units on a scale STANDARD_DEVIATION 0.92 | 9.25 units on a scale STANDARD_DEVIATION 0.7 | 8.90 units on a scale STANDARD_DEVIATION 0.99 | 9.16 units on a scale STANDARD_DEVIATION 0.75 | 8.50 units on a scale STANDARD_DEVIATION 0.92 |
| Absolute Value of Scores for Dyadic Coping Strategies | 40.11 units on a scale STANDARD_DEVIATION 2.47 | 40.07 units on a scale STANDARD_DEVIATION 2.26 | 38.87 units on a scale STANDARD_DEVIATION 2.65 | 40.25 units on a scale STANDARD_DEVIATION 2.56 | 42.50 units on a scale STANDARD_DEVIATION 1.6 | 39.70 units on a scale STANDARD_DEVIATION 2.9 | 40.66 units on a scale STANDARD_DEVIATION 1.63 | 40.12 units on a scale STANDARD_DEVIATION 1.64 |
| Absolute Value of Scores for Environment Subscale of World Health Organization Quality of Life Bref | 9.38 units on a scale STANDARD_DEVIATION 1.02 | 9.28 units on a scale STANDARD_DEVIATION 1.06 | 8.68 units on a scale STANDARD_DEVIATION 0.79 | 9.68 units on a scale STANDARD_DEVIATION 0.79 | 10.25 units on a scale STANDARD_DEVIATION 0.88 | 9.40 units on a scale STANDARD_DEVIATION 0.96 | 10.00 units on a scale STANDARD_DEVIATION 0.89 | 9.00 units on a scale STANDARD_DEVIATION 1.19 |
| Absolute Value of Scores for High Risk Perinatal Distress (Anxiety and Depression) | 57.93 units on a scale STANDARD_DEVIATION 4.41 | 60.21 units on a scale STANDARD_DEVIATION 2.96 | 59.06 units on a scale STANDARD_DEVIATION 3.15 | 59.18 units on a scale STANDARD_DEVIATION 2.85 | 58.75 units on a scale STANDARD_DEVIATION 3.28 | 52.70 units on a scale STANDARD_DEVIATION 5.27 | 51.66 units on a scale STANDARD_DEVIATION 2.33 | 59.62 units on a scale STANDARD_DEVIATION 3.88 |
| Absolute Value of Scores for Perceived Social Support | 19.28 units on a scale STANDARD_DEVIATION 2.59 | 20.07 units on a scale STANDARD_DEVIATION 3.02 | 20.06 units on a scale STANDARD_DEVIATION 2.76 | 18.31 units on a scale STANDARD_DEVIATION 1.99 | 21.00 units on a scale STANDARD_DEVIATION 2 | 17.50 units on a scale STANDARD_DEVIATION 1.58 | 19.16 units on a scale STANDARD_DEVIATION 3.31 | 18.87 units on a scale STANDARD_DEVIATION 2.03 |
| Absolute Value of Scores for Physical Subscale of World Health Organization Quality of Life Bref | 9.65 units on a scale STANDARD_DEVIATION 1.28 | 9.21 units on a scale STANDARD_DEVIATION 1.36 | 9.75 units on a scale STANDARD_DEVIATION 1.23 | 9.56 units on a scale STANDARD_DEVIATION 1.31 | 10.62 units on a scale STANDARD_DEVIATION 0.91 | 9.70 units on a scale STANDARD_DEVIATION 1.33 | 9.66 units on a scale STANDARD_DEVIATION 0.81 | 9.37 units on a scale STANDARD_DEVIATION 1.59 |
| Absolute Value of Scores for Social Subscale of World Health Organization Quality of Life Bref | 3.66 units on a scale STANDARD_DEVIATION 0.61 | 3.50 units on a scale STANDARD_DEVIATION 0.61 | 3.87 units on a scale STANDARD_DEVIATION 0.61 | 3.43 units on a scale STANDARD_DEVIATION 0.62 | 3.75 units on a scale STANDARD_DEVIATION 0.7 | 3.70 units on a scale STANDARD_DEVIATION 0.48 | 3.50 units on a scale STANDARD_DEVIATION 0.54 | 4.00 units on a scale STANDARD_DEVIATION 0.75 |
| Absolute Value of Scores for Wellbeing | 10.66 units on a scale STANDARD_DEVIATION 1.99 | 11.14 units on a scale STANDARD_DEVIATION 2.07 | 11.12 units on a scale STANDARD_DEVIATION 2.12 | 10.50 units on a scale STANDARD_DEVIATION 2.28 | 11.37 units on a scale STANDARD_DEVIATION 1.68 | 9.80 units on a scale STANDARD_DEVIATION 1.75 | 10.33 units on a scale STANDARD_DEVIATION 1.63 | 9.87 units on a scale STANDARD_DEVIATION 1.64 |
| Age, Continuous | 30.56 years STANDARD_DEVIATION 4.3 | 30.35 years STANDARD_DEVIATION 3.83 | 30.37 years STANDARD_DEVIATION 4.06 | 30.68 years STANDARD_DEVIATION 4.98 | 30.50 years STANDARD_DEVIATION 4.37 | 28.25 years STANDARD_DEVIATION 3.01 | 34.33 years STANDARD_DEVIATION 6.15 | 30.62 years STANDARD_DEVIATION 2.97 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 78 Participants | 14 Participants | 16 Participants | 16 Participants | 8 Participants | 10 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Pakistan | 78 participants | 14 participants | 16 participants | 16 participants | 8 participants | 10 participants | 6 participants | 8 participants |
| Sex: Female, Male Female | 39 Participants | 7 Participants | 8 Participants | 8 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants |
| Sex: Female, Male Male | 39 Participants | 7 Participants | 8 Participants | 8 Participants | 4 Participants | 5 Participants | 3 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 14 | 0 / 0 | 0 / 0 | 0 / 8 | 0 / 10 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 3 / 14 | 0 / 0 | 0 / 0 | 2 / 8 | 2 / 10 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 14 | 0 / 0 | 0 / 0 | 0 / 8 | 0 / 10 | 0 / 0 | 0 / 0 |
Outcome results
Primary
The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale
The Generalized Anxiety Disorder Subscale and Major Depressive Disorder Subscale comprised 8 and 14 items respectively in Parental Perinatal Distress Scale. The response categories range from 0 to 3 scale. The total number of items in both subscales is 22. The summed scores obtained on 22 items range from 0 (minimum) to 66 (maximum). The high total score indicates worse symptoms of perinatal distress in the couples. In the present study, data mean and standard deviation specify absolute value at a pre-test and post-test assessment.
Time frame: After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion.
Population: The target enrollment was met and planned statistical analyses were performed. The impact of treatment (psychopharmacological medicine; CBCT; CBCT along with Zikr; combined (Psychopharmacological medicine and CBCT); combined (Psychopharmacological and CBCT along with Zikr), placebo comparator, and no intervention is measured for perinatal distress via ANCOVA after controlling for baseline pre-test scores for perinatal distress (depression and anxiety) and monthly income in SPSS-24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psychopharmacological Intervention | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 18.14 score on a scale | Standard Deviation 2.03 |
| CBCT Without Zikr Intervention | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 17.31 score on a scale | Standard Deviation 2.33 |
| CBCT With Zikr Intervention | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 15.62 score on a scale | Standard Deviation 2.47 |
| Combined Intervention Without Zikr | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 8.62 score on a scale | Standard Deviation 1.5 |
| Combined Intervention With Zikr | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 9.50 score on a scale | Standard Deviation 1.35 |
| Placebo Comparator | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 53.33 score on a scale | Standard Deviation 2.87 |
| No Intervention | The Sum of Scores of Major Depressive Disorder Subscale and Generalized Anxiety Disorder Subscale | 60.12 score on a scale | Standard Deviation 4.12 |
p-value: 090% CI: [-38.9, -32.19]ANCOVA
Primary
The Sum of Scores on Dyadic Coping Inventory (DCI)
Dyadic Coping Inventory comprised 37 items with 1 to 5 scoring categories. However, items 36 and 37 were not included in the scoring as these were evaluative items. The sum of scores for the remaining 35 items range from 35 (minimum) to 175 (maximum). The high score indicates better-than-average levels of coping skills in perinatal couples. In the present study, data mean and standard deviation specifies absolute values in post-test assessment.
Time frame: After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion.
Population: The target enrollment was met and planned statistical analyses were performed. The impact of treatment (psychopharmacological medicine; CBCT; CBCT along with Zikr; combined (Psychopharmacological medicine and CBCT); combined (Psychopharmacological and CBCT along with Zikr), placebo comparator, and no intervention is measured for dyadic coping via ANCOVA after controlling for baseline pre-test scores for perinatal distress (depression and anxiety) and monthly income in SPSS-24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psychopharmacological Intervention | The Sum of Scores on Dyadic Coping Inventory (DCI) | 105.42 score on a scale | Standard Deviation 2.97 |
| CBCT Without Zikr Intervention | The Sum of Scores on Dyadic Coping Inventory (DCI) | 153.25 score on a scale | Standard Deviation 1.77 |
| CBCT With Zikr Intervention | The Sum of Scores on Dyadic Coping Inventory (DCI) | 155.93 score on a scale | Standard Deviation 3.83 |
| Combined Intervention Without Zikr | The Sum of Scores on Dyadic Coping Inventory (DCI) | 161.37 score on a scale | Standard Deviation 3.24 |
| Combined Intervention With Zikr | The Sum of Scores on Dyadic Coping Inventory (DCI) | 162.40 score on a scale | Standard Deviation 4.9 |
| Placebo Comparator | The Sum of Scores on Dyadic Coping Inventory (DCI) | 41.16 score on a scale | Standard Deviation 1.16 |
| No Intervention | The Sum of Scores on Dyadic Coping Inventory (DCI) | 40.25 score on a scale | Standard Deviation 1.48 |
p-value: 090% CI: [78.33, 95.46]ANCOVA
Primary
The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF)
World Health Organization Quality of Life Bref (WHOQOL-BREF) comprised 26 items with 1 to 5 scoring categories. Item 1 and item 2 were not included in the scoring domains because these were evaluative items. The remaining 24 items are classified in four subscales (physical, psychological, social, and environmental) of quality of life. Sum of scores for physical aspect (7 items) of life ranged from 7 (minimum) to 35 (maximum); 6(minimum) to 30 (maximum) for psychological subscale (6 items); 3 (minimum) to 20 (maximum) for social subscale(3 items); and 8 (minimum) to 40 (maximum) for environmental subscale (8 items) of life. The high score indicates a better quality of life in that particular subscale domain in perinatal couples. In the present study, data mean and standard deviation specifies absolute values in pre-test and post-test assessment.
Time frame: After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion.
Population: Target enrollment was met, planned statistical analyses were performed. The impact of treatment (psychopharmacological; CBCT; CBCT along with Zikr; combined (Psychopharmacological and CBCT); combined (Psychopharmacological and CBCT along with Zikr), placebo comparator, and no intervention is measured for physical, psychological, social, and environmental quality of life via ANCOVA after controlling for pre-test scores for perinatal distress (depression and anxiety) and monthly income in SPSS-24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Psychopharmacological Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 28.64 score on a scale | Standard Deviation 1.08 |
| Psychopharmacological Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 29.07 score on a scale | Standard Deviation 2.12 |
| Psychopharmacological Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 37.92 score on a scale | Standard Deviation 1.14 |
| Psychopharmacological Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 13.50 score on a scale | Standard Deviation 0.75 |
| CBCT Without Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 28.37 score on a scale | Standard Deviation 1.2 |
| CBCT Without Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 38.31 score on a scale | Standard Deviation 1.13 |
| CBCT Without Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 29.12 score on a scale | Standard Deviation 2.02 |
| CBCT Without Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 13.56 score on a scale | Standard Deviation 0.96 |
| CBCT With Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 30.06 score on a scale | Standard Deviation 3.02 |
| CBCT With Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 29.06 score on a scale | Standard Deviation 0.92 |
| CBCT With Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 13.93 score on a scale | Standard Deviation 0.92 |
| CBCT With Zikr Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 38.18 score on a scale | Standard Deviation 1.1 |
| Combined Intervention Without Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 13.50 score on a scale | Standard Deviation 0.92 |
| Combined Intervention Without Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 29.50 score on a scale | Standard Deviation 2.07 |
| Combined Intervention Without Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 37.87 score on a scale | Standard Deviation 1.12 |
| Combined Intervention Without Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 28.75 score on a scale | Standard Deviation 1.03 |
| Combined Intervention With Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 30.20 score on a scale | Standard Deviation 1.93 |
| Combined Intervention With Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 28.80 score on a scale | Standard Deviation 1.22 |
| Combined Intervention With Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 13.90 score on a scale | Standard Deviation 0.99 |
| Combined Intervention With Zikr | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 38.70 score on a scale | Standard Deviation 0.94 |
| Placebo Comparator | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 9.66 score on a scale | Standard Deviation 0.51 |
| Placebo Comparator | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 10.00 score on a scale | Standard Deviation 0.89 |
| Placebo Comparator | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 3.66 score on a scale | Standard Deviation 0.99 |
| Placebo Comparator | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 10.16 score on a scale | Standard Deviation 0.75 |
| No Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Physical Subscale | 10.50 score on a scale | Standard Deviation 1.41 |
| No Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Social Subscale | 4.12 score on a scale | Standard Deviation 0.64 |
| No Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Psychological Subscale | 9.25 score on a scale | Standard Deviation 0.7 |
| No Intervention | The Sum of Scores on Each Subscale of World Health Organization Quality of Life (WHOQOL-BREF) | Post Test Assessment on Environmental Subscale | 9.62 score on a scale | Standard Deviation 0.74 |
Comparison: Physical Domain of Quality of Lifep-value: 090% CI: [15.02, 17.87]ANCOVA
Comparison: Psychological Domain of Quality of Lifep-value: 090% CI: [15.16, 18.04]ANCOVA
Comparison: Social Domain of Quality of Lifep-value: 090% CI: [7.52, 9.01]ANCOVA
p-value: 090% CI: [21.64, 25.81]ANCOVA
Primary
The Sum of Scores on Flourishing Scale (FS)
The Flourishing Scale comprised 8 items with 1 to 7 scoring categories. Sum of scores range from 8 (minimum) to 56 (maximum) for eight items. The high score indicates better well-being in perinatal couples. In the present study, data mean and standard deviation specifies absolute values in pre-test and post-test assessment.
Time frame: After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion.
Population: The target enrollment was met and planned statistical analyses were performed. The impact of treatment (psychopharmacological medicine; CBCT; CBCT along with Zikr; combined (Psychopharmacological medicine and CBCT); combined (Psychopharmacological and CBCT along with Zikr), placebo comparator, and no intervention is measured for perceived wellbeing via ANCOVA after controlling for baseline pre-test scores for perinatal distress (depression and anxiety) and monthly income in SPSS-24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psychopharmacological Intervention | The Sum of Scores on Flourishing Scale (FS) | 19.78 score on a scale | Standard Deviation 3.4 |
| CBCT Without Zikr Intervention | The Sum of Scores on Flourishing Scale (FS) | 38.56 score on a scale | Standard Deviation 1.89 |
| CBCT With Zikr Intervention | The Sum of Scores on Flourishing Scale (FS) | 38.31 score on a scale | Standard Deviation 2.33 |
| Combined Intervention Without Zikr | The Sum of Scores on Flourishing Scale (FS) | 52.37 score on a scale | Standard Deviation 2.97 |
| Combined Intervention With Zikr | The Sum of Scores on Flourishing Scale (FS) | 50.80 score on a scale | Standard Deviation 2.57 |
| Placebo Comparator | The Sum of Scores on Flourishing Scale (FS) | 9.83 score on a scale | Standard Deviation 1.6 |
| No Intervention | The Sum of Scores on Flourishing Scale (FS) | 9.50 score on a scale | Standard Deviation 1.51 |
p-value: 090% CI: [19.41, 25.12]ANCOVA
Primary
The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS)
The Multidimensional Scale for Perceived Social Support comprised 12 items. There are 1 to 7 scoring categories. The sum of score for 12 items range from 12 (minimum) to 84 (maximum). The high score indicates better social support for perinatal couples. In the present study, data mean and standard deviation specifies absolute values in post-test assessment.
Time frame: After recruitment, screening, randomization, and allocation, Pre-test Assessment on week 1 (Baseline Measures) and post-test assessment on week 10 (Outcome Measures) through the study period completion.
Population: The target enrollment was met and planned statistical analyses were performed. The impact of treatment (psychopharmacological medicine; CBCT; CBCT along with Zikr; combined (Psychopharmacological medicine and CBCT); combined (Psychopharmacological and CBCT along with Zikr), placebo comparator, and no intervention is measured for perceived social support via ANCOVA after controlling for baseline pre-test scores for perinatal distress (depression and anxiety) and monthly income in SPSS-24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Psychopharmacological Intervention | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 22.14 score on a scale | Standard Deviation 1.4 |
| CBCT Without Zikr Intervention | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 38.31 score on a scale | Standard Deviation 4.4 |
| CBCT With Zikr Intervention | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 47.00 score on a scale | Standard Deviation 2 |
| Combined Intervention Without Zikr | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 79.00 score on a scale | Standard Deviation 3.2 |
| Combined Intervention With Zikr | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 80.50 score on a scale | Standard Deviation 2.63 |
| Placebo Comparator | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 18.66 score on a scale | Standard Deviation 3.32 |
| No Intervention | The Sum of Scores on Multidimensional Scale for Perceived Social Support (MSPSS) | 18.62 score on a scale | Standard Deviation 1.59 |
p-value: 090% CI: [19.59, 28.32]ANCOVA
Secondary
Changes in Blood Concentration (Either ng/ml or mg/L) Levels for Escitalopram and Sertraline
Gynaecologist prescribed 5 mg/day escitalopram antenatally or 12.5 mg/day sertraline postnatally. Assessment of blood concentration level via High Performance Liquid Chromatography was conditioned on consent of the participants. The overall number of participants analyzed in Secondary Outcome Period Participants (1st Oct to 28 Oct) represent the total number of participants from the Primary Outcome Period, for each Arm/Group. The data were not collected and the outcome cannot be reported for arms without psychopharmacological intervention including 0 participants. The participants withdrew from HPLC to avoid expansive biomedical tests, adhering to Pakistani cultural norm. The toxicity levels is not reported in the blood of the couples because 5 mg/day escitalopram (Eichentopf et al; Bellantuono et al) or 12.5 mg/day sertraline (Almurjan et al ; Heinonen et al) and is considered safe dose range with no sign of toxicity in blood concentration levels and no presence of adverse events.
Time frame: After recruitment, screening, randomization, and allocation, changes in blood concentration levels for Escitalopram and Sertraline as assessed on week 12 (follow-up) through the study period (two and half months).
Population: No medicine was prescribed in CBCT (with, without Zikr), placebo, and no intervention arms and N/A indicate absence of assessment in these arms. The subjects withdraw from blood test consent in psychopharmacological arm, combined intervention with zikr arm, and combined intervention without zikr arm and Zero specified the absence of assessment of blood concentration levels (5 mg escitalopram or 12.5 mg sertraline) due to participants' withdrawal.
Secondary
Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0
Side effects of escitalopram and sertraline (5 mg/day, and 12.5 mg/day respectively) classified as Grade 1 level in CTCAE v4.0 as these settle down within two to three weeks of medication. A checklist assessed presence or absence of adverse events among participants in psychopharmacological intervention arm, combined intervention without zikr arm, and combined intervention with zikr arm qualitatively. The overall number of participants analyzed in Secondary Outcome Period Participants (1st Oct to 28 Oct) represent the total number of participants for whom an Outcome Measure was measured and analyzed from the Primary Outcome Period Participants, for each Arm/Group. The data were not collected and the outcome cannot be reported for arms without psychopharmacological intervention including 0 participants analyzed because medication was not administered.
Time frame: After recruitment, screening, randomization, and allocation, number of participants with treatment-related adverse events as assessed by CTCAE v4.0 on week 11 and week 12 (follow-ups) through the study period (two and half months).
Population: Adverse events (AE) were not assessed for CBCT (Without or With Zikr), Placebo \& No Intervention Arms; 0 specified absence. AE were assessed systematically with checklist in psychopharmacology \& combined arms (with, without Zikr); Zero specified absence of all-cause mortality and serious AE. Total Number of Participants at Risk showed Participant Flow module count. Other (non-serious) AE, mild transitional side effects (nausea, stomachache) were reported with frequency threshold above 5%.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Psychopharmacological Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 2 Participants |
| Psychopharmacological Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 1 Participants |
| CBCT Without Zikr Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 0 Participants |
| CBCT Without Zikr Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 0 Participants |
| CBCT With Zikr Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 0 Participants |
| CBCT With Zikr Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 0 Participants |
| Combined Intervention Without Zikr | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 1 Participants |
| Combined Intervention Without Zikr | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 1 Participants |
| Combined Intervention With Zikr | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 1 Participants |
| Combined Intervention With Zikr | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 1 Participants |
| Placebo Comparator | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 0 Participants |
| Placebo Comparator | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 0 Participants |
| No Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Nausea | 0 Participants |
| No Intervention | Number of Participants With Treatment-related Adverse Events as Assessed by CTCAE v4.0 | Other [Not Including Serious] Adverse Events: Stomach Pain | 0 Participants |