Erectile Dysfunctions, Hypoactive Sexual Desire Disorder, Sexual Dysfunctions, Psychological
Conditions
Keywords
sexual dysfunctions, erectile dysfunctions, hypoactive sexual desire dysfunctions
Brief summary
The purpose of this study is to assess the tolerability, safety, and efficacy of bupropion hydrochloride sustained-release in the treatment of sexual dysfunction in men on methadone maintenance therapy.
Detailed description
This is a single-center (University Malaya Medical Centre), randomized, double-Blind, placebo-controlled versus bupropion hydrochloride sustained-releases study trial on 70 men who have methadone emergent sexual dysfunction. Bupropion hydrochloride sustained-release (Wellbutrin SR) 150mg once a day for 7 days then 150mg twice a day for 42 days. Taken orally by the subjects.The total duration of the study is expected to be 24 months. 20months for subject recruitment and 4 months for final subject follow-up. The primary endpoint is Mean improvement in scores on the Clinical Global Impression Scale adapted for sexual Function (CGI-SF). Secondary endpoints are Change from baseline International Index of Erectile Function (IIEF-15) score. Mean improvement in scores on the sexual desire inventory 2 (SDI2). Other evaluation included: Montgomery-Åsberg Depression Rating Scale (MADRS- Malay version ), Mini International Neuropsychiatric Interview (M.I.N.I), Opiate Treatment Index (OTI), World health organization Quality of Life-Brief Scale (WHOQoL-Brief, Malay version), Malay Version of the Golombok-Rust Inventory of Marital State (Mal-GRIMS) and Rapid urine drug test. Safety evaluation included: Incidence of adverse events. Data will be analyzed using linear mixed-effects model.
Interventions
DRUGBupropion hydrochloride sustained-release
Up to 70 eligible patients will be randomly assigned to Bupropion Hydrochloride Sustained-Release or placebo treatment groups in a 1:1 ratio using a computer-generated table of random numbers through the use of the Randomization.com program. Subjects will be randomized to to Bupropion Hydrochloride Sustained-Release 150mg b.d. (n = 35) or placebo b.d (n = 35)The study drug will be repacked in the standard capsules by the research assistant who is not involved in the assessment of the study. The study drug and placebo will be packaged in sets of 11 (1 tablet per day for 3 days, followed by 2 tablets per day for 4 days.) for the first week. Subsequently, the study drug and placebo will be packaged in sets of 14 (2 tablets per day for 7 days.).
DRUGplacebo
Up to 70 eligible patients will be randomly assigned to Bupropion Hydrochloride Sustained-Release or placebo treatment groups in a 1:1 ratio using a computer-generated table of random numbers through the use of the Randomization.com program. Subjects will be randomized to to Bupropion Hydrochloride Sustained-Release 150mg b.d. (n = 35) or placebo b.d (n = 35)
Sponsors
University of Malaya
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Had a diagnosis of opioid dependence base on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria * While taking a stable dose of methadone In UMMC (University Malaya Medica Centre) and University Malaya centre of Addiction Science (UMCAS) outpatient clinic for ≥ 6 months * Were experiencing constant sexual dysfunction for ≥ 4 weeks * Were in a stable sexual relationship with a female partner for ≥ 6 months
Exclusion criteria
* Severe behavior disturbances or psychotic symptoms * Obvious organic illnesses caused the sexual dysfunction (such as diabetics or patients with heart and vascular disease) * Those with history of sexual dysfunction before methadone therapy * Receiving antiviral treatment for viral hepatitis or HIV, or androgen replacement treatment. * History of an eating disorder (eg, anorexia, bulimia) or seizures (eg, epilepsy) * Using other psychotropic medications other than methadone * Clinical significant abnormal laboratory values. * Clinically significant abnormal ECG. Documented history of other psychiatric diagnosis (schizophrenia, bipolar disorder, major depressive disorder, organic brain disorder, dementia etc.) * Refused to give participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Score of ≤2 (Much/Very Much Improved) on the Clinical Global Impression Scale Adapted for Sexual Function (CGI-SF) at Week 6 Between Placebo and Active Group | assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported | This scale assesses the changes of the sexual function. Scores range from 1 (normal/very much improved) to 7 (most extreme sexual dysfunction/very much worse). Lower scores indicate better sexual functioning. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported | Mal-IIEF-15 is a 15-item, multi-dimensional self-reporting instrument for the evaluation of male sexual function for the past 4 weeks, consisted of five domains; 1) Erectile Function: sum of items 1, 2, 3, 4, 5 & 15. Total score range =1-30. 2) Orgasmic Function: sum of items 9 and 10. Total score range = 0 -10. 3) Sexual Desire: sum of items 11 and 12. Total score range = 2 -10. 4) Intercourse Satisfaction : sum of scores for Questions 6, 7 and 8. Total score range = 0 -15. 5) Overall Satisfaction: sum of items 13 and 14.Total score range = 2 -10. Items 1-10 is 6-point Likert-type scale from '0' (= No sexual activity) to '5' (= Almost always or always). Items 11-15 is 5-point Likert-type scale from '1' (= Almost never or never) to '5 '(= 'Almost always or always').The total Mal-IIEF-15 range from 5 (minimum) to 75 (Maximum). Higher score indicates better outcome in all domain. |
| Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | Assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported | This scale contains 14 items which yield two domain scores: dyadic sexual desire (DSD) and solitary sexual desire (SSD). Items 1,2, 10, 14 are 8-point Likert scale from '0' (= not at all) to '7' (= more than once a day) concerning frequency of desire. Remaining Items are 9-point Likert scale from '0' (= 'no desire') to '8' (= 'strong desire'). DSD has 8 items and SSD has 3 items. The total sores for DSD range from 0 to 62, and SSD, range from 0 to 23. All items are summed up to dictate the total sexual desire (total score = 0 to 112). Higher scores reflect higher sexual desire. |
Countries
Malaysia
Participant flow
Recruitment details
All the male subjects who attended the methadone maintenance clinic from December 2015 to December 2017 in University Malaya Medical Center (UMMC) and University Malaya Center of Addiction Science Studies (UMCAS) were approached.Screening data was reviewed to determine subject eligibility.
Pre-assignment details
This study screened 109 and included 80 (73.4%) male patients who met all inclusion criteria and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo BD | 40 |
| Active Bupropion hydrochloride sustained-release 150mg BD | 40 |
| Total | 80 |
Baseline characteristics
| Characteristic | Placebo | Active | Total |
|---|---|---|---|
| Age, Continuous | 43.50 years STANDARD_DEVIATION 10.09 | 42.30 years STANDARD_DEVIATION 9.49 | 42.83 years STANDARD_DEVIATION 9.68 |
| Malay version of International Index of Erectile Function (Mal-IIEF-15) | 42.44 units on a scale STANDARD_DEVIATION 16.43 | 41.80 units on a scale STANDARD_DEVIATION 19.13 | 42.12 units on a scale STANDARD_DEVIATION 17.78 |
| Race/Ethnicity, Customized Race Chinese | 5 Participants | 3 Participants | 8 Participants |
| Race/Ethnicity, Customized Race Indian | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Race Malay | 34 Participants | 34 Participants | 68 Participants |
| Race/Ethnicity, Customized Race Others | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 40 Participants | 40 Participants | 80 Participants |
| Total Malay version of the SDI-2 (SDI-2-BM) | 42.87 units on a scale STANDARD_DEVIATION 15.83 | 42.58 units on a scale STANDARD_DEVIATION 14.97 | 42.73 units on a scale STANDARD_DEVIATION 15.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 8 / 36 | 13 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 |
Outcome results
Primary
Number of Participants With a Score of ≤2 (Much/Very Much Improved) on the Clinical Global Impression Scale Adapted for Sexual Function (CGI-SF) at Week 6 Between Placebo and Active Group
This scale assesses the changes of the sexual function. Scores range from 1 (normal/very much improved) to 7 (most extreme sexual dysfunction/very much worse). Lower scores indicate better sexual functioning.
Time frame: assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported
Population: Intention-to-treat (ITT) analyses were used for all efficacy variables and included all patients who had been randomized, took at least 1 dose of study trial medication and had at least one efficacy assessment after the baseline visit. There were four patients in each arm did not come for first efficacy assessment, Hence, excluded from analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With a Score of ≤2 (Much/Very Much Improved) on the Clinical Global Impression Scale Adapted for Sexual Function (CGI-SF) at Week 6 Between Placebo and Active Group | 10 Participants |
| Active | Number of Participants With a Score of ≤2 (Much/Very Much Improved) on the Clinical Global Impression Scale Adapted for Sexual Function (CGI-SF) at Week 6 Between Placebo and Active Group | 21 Participants |
Secondary
Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group
Mal-IIEF-15 is a 15-item, multi-dimensional self-reporting instrument for the evaluation of male sexual function for the past 4 weeks, consisted of five domains; 1) Erectile Function: sum of items 1, 2, 3, 4, 5 & 15. Total score range =1-30. 2) Orgasmic Function: sum of items 9 and 10. Total score range = 0 -10. 3) Sexual Desire: sum of items 11 and 12. Total score range = 2 -10. 4) Intercourse Satisfaction : sum of scores for Questions 6, 7 and 8. Total score range = 0 -15. 5) Overall Satisfaction: sum of items 13 and 14.Total score range = 2 -10. Items 1-10 is 6-point Likert-type scale from '0' (= No sexual activity) to '5' (= Almost always or always). Items 11-15 is 5-point Likert-type scale from '1' (= Almost never or never) to '5 '(= 'Almost always or always').The total Mal-IIEF-15 range from 5 (minimum) to 75 (Maximum). Higher score indicates better outcome in all domain.
Time frame: assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported
Population: Intention-to-treat (ITT) analyses were used for all efficacy variables and included all patients who had been randomized, took at least 1 dose of study trial medication and had at least one efficacy assessment after the baseline visit. There were four patients in each arm did not come for first efficacy assessment, Hence, excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Intercourse satisfaction domain | 6.46 score on a scale | Standard Deviation 4.18 |
| Placebo | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Overall satisfaction domain | 7.14 score on a scale | Standard Deviation 2.41 |
| Placebo | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | IIEF total | 43.81 score on a scale | Standard Deviation 19.86 |
| Placebo | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Erectile function domain | 18.06 score on a scale | Standard Deviation 9.43 |
| Placebo | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Orgasmic function domain | 5.99 score on a scale | Standard Deviation 3.75 |
| Placebo | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Sexual desire domain | 6.04 score on a scale | Standard Deviation 1.97 |
| Active | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | IIEF total | 52.53 score on a scale | Standard Deviation 16.14 |
| Active | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Intercourse satisfaction domain | 8.78 score on a scale | Standard Deviation 3.77 |
| Active | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Orgasmic function domain | 7.30 score on a scale | Standard Deviation 2.92 |
| Active | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Overall satisfaction domain | 7.10 score on a scale | Standard Deviation 2.29 |
| Active | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Sexual desire domain | 6.77 score on a scale | Standard Deviation 1.91 |
| Active | Mean Difference of Malay Version of International Index of Erectile Function (Mal-IIEF-15) at Week 6 Between Placebo and Active Group | Mal-IIEF-15, Erectile function domain | 22.56 score on a scale | Standard Deviation 7.69 |
Secondary
Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups
This scale contains 14 items which yield two domain scores: dyadic sexual desire (DSD) and solitary sexual desire (SSD). Items 1,2, 10, 14 are 8-point Likert scale from '0' (= not at all) to '7' (= more than once a day) concerning frequency of desire. Remaining Items are 9-point Likert scale from '0' (= 'no desire') to '8' (= 'strong desire'). DSD has 8 items and SSD has 3 items. The total sores for DSD range from 0 to 62, and SSD, range from 0 to 23. All items are summed up to dictate the total sexual desire (total score = 0 to 112). Higher scores reflect higher sexual desire.
Time frame: Assessed at baseline, day 14(week 2), day 28(week four) and day 42 (week 6), data at day 42 (week 6) reported
Population: Intention-to-treat (ITT) analyses were used for all efficacy variables and included all patients who had been randomized, took at least 1 dose of study trial medication and had at least one efficacy assessment after the baseline visit. There were four patients in each arm did not come for first efficacy assessment, Hence, excluded from analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | SDI-2 | 47.36 score on a scale | Standard Deviation 21.09 |
| Placebo | Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | DSD | 29.99 score on a scale | Standard Deviation 13.44 |
| Placebo | Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | SSD | 6.87 score on a scale | Standard Deviation 5.97 |
| Active | Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | SDI-2 | 53.53 score on a scale | Standard Deviation 15.88 |
| Active | Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | DSD | 36.08 score on a scale | Standard Deviation 10.17 |
| Active | Mean Difference of Malay Version of Sexual Desire Inventory 2 (SDI-2) Score at Weeks 6 Between Placebo and Active Groups | SSD | 7.45 score on a scale | Standard Deviation 4.97 |