Functional Abdominal Pain, Functional Dyspepsia, Irritable Bowel Syndrome, Functional Gastrointestinal Disorders
Conditions
Keywords
Functional Pain, Abdominal Pain, Irritable Bowel Syndrome, IBS, Functional Dyspepsia, FGID, Functional Gastrointestinal Disorders
Brief summary
This study is aimed at investigating the efficacy of placebo for symptom relief in children with abdominal pain related functional gastrointestinal disorders.
Detailed description
The purpose of this research study is to see if prescribing an open label placebo to children with functional gastrointestinal disorders will help improve symptoms and their overall quality of life. Open label means you/your child are aware you are taking liquid placebo drops and not an active medication. Symptoms associated with functional gastrointestinal disorders (FGIDs) of children and adolescents are commonly encountered symptoms in general pediatrics and pediatric gastroenterology. The FGIDs the investigators are studying include functional abdominal pain, irritable bowel syndrome, and functional dyspepsia. The liquid placebo drops contain no active medication. Recent research studies have shown improvement in gastrointestinal symptoms after taking liquid placebo drops in both children and adults with FGIDs. A randomized research study for a medication used to treat children with FGIDs showed a very significant placebo effect, meaning patients receiving placebo also experienced improvement in their symptoms. Randomized refers to the fact that subjects were randomly selected to receive either the study medication or placebo. A recent adult study gave adult patients a placebo and told them it was a placebo, and these adults also had significant symptom improvement. The goal of this study is to further explore using open label (or non-deceptive) placebo use to treat children with FGIDs.
Interventions
OTHERPlacebo Suspension
The study is divided into three phases: 1 one-week baseline assessment followed by 2 three-week study phases (phase A and phase B). Phase A will require subjects to take 1/4 teaspoon placebo suspension 2 times a day (morning and night), and a third dose if necessary. In phase B subjects will not take the placebo. After 3 weeks in initial phase (either Phase A or B), subjects will switch to the alternate phase and continue the study for another 3 weeks. Hyoscyamine is available as a rescue medication during Phase A and Phase B. Half of the subjects will be randomized to begin with Phase A and half will be randomized to begin with Phase B.
DRUGHyoscyamine
While not an intervention of interest to our study, patients will have hyoscyamine available as a rescue medication throughout the study. This can be taken on a PRN basis for breakthrough pain a maximum of 4x daily.
Sponsors
Nationwide Children's Hospital
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open placebo. No masking
Eligibility
Sex/Gender
ALL
Age
8 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
1. Age 8 to 21 years. 2. Diagnosis of functional abdominal pain, irritable bowel syndrome or functional dyspepsia made by a pediatric gastroenterologist according to Rome III Criteria. 3. Mean daily intensity of pain of 25 mm in the week prior to the initiation of the study, based on the Visual Analogue Scale 4. Children will not be excluded if they are adhering to any specific diet. Children will be asked to report any specific established diet prior to the study or dietary modifications that could have been made during the course of the study. 5. Normal laboratory tests including complete blood count, erythrocyte sedimentation rate, albumin, serum amylase, lipase, liver enzymes, urine analysis, stool examination for occult blood and ova and parasites one month prior the initiation of the study. Urinary culture will be obtained if the symptoms or urinalysis suggest the possibility of a urinary infection. 6. Normal lactose breath test or history of lack of resolution of symptoms on a lactose-free diet (2 weeks). 7. Patients receiving psychological treatment, hypnosis, biofeedback or guided imagery will not be excluded of the study if those were started at least one month prior to the initiation of the study and are not planned to be discontinued during the length of the trial. Patients will need to be prescribed hyoscyamine (clinically indicated) to be considered for this study, as the placebo will be in addition to their prescribed medication.
Exclusion criteria
1. Inclusion criteria not met. 2. Evidence of organic gastrointestinal disease, hepatic disorders, urinary or cardiac disease. 3. Children below the 5th percentile for weight or height. 4. Hemoccult positive stools. 5. Patients with diagnosis of Inflammatory Bowel Disease, hyperthyroidism, CHF, cardiac arrhythmias, prostatic hypertrophy, autonomic neuropathy, biliary tract disease, children with spastic paralysis or chronic lung disease (we will consult a pulmonologist concerning the inclusion of children with chronic lung disease). 6. Patients who are taking any of the following drugs: AbobotulinumtoxinA, Acetylcholinesterase Inhibitors (Central), Cannabinoids, OnabotulinumtoxinA, Potassium Chloride, Pramlintide, RimabotulinumtoxinB, Secretin. Patients receiving antidepressant or anticholinergic drugs will be excluded from the study. PPIs will be allowed as long as the patient had been on a stable dose for at least 12 weeks. 7. Patients planning to change their diet during the time of the study will be excluded. Children will be asked to report any specific established diet prior to the study or dietary modifications that could have been made during the course of the study. 8. Patients planning to start psychological treatment, hypnosis, biofeedback, or guided imagery during the course of the study or have started any of these within the month prior to consent. 9. The participant is pregnant or is planning to become pregnant throughout the course of the research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Primary Outcome Measure Was Mean Daily Pain | It will be assessed at the end of the 3-week and 6-week treatment periods (at the end of each treatment arm prior to crossover to the next arm of treatment) | Change in mean pain score comparing both treatment arms to the baseline using the Visual analogue scale. (Scale 0-100mm) The scale reflects severity of the pain going from no pain (0) to maximum pain (100mm). Therefore the higher the number the more severe the pain is |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Use of Rescue Medications | 3 weeks of placebo vs 3 weeks of no treatment | The number of medications used as rescue during each one of the periods of the study were counted |
| Clinical Global Improvement | Following 1-week baseline and 3-week and 6-week treatment periods | Compared clinical global improvement during each phase of the study The following question was used: Overall, how do you feel your problem is? (better, same, or worse). Patients were then divided in 2 groups: improved (if they answered better) vs not improved (if they answered same/worse) |
Countries
United States
Participant flow
Pre-assignment details
Cross over study
Participants by arm
| Arm | Count |
|---|---|
| Placebo First Followed by no Treatment Arm 1: Subjects take 1/4 teaspoon placebo suspension 2 times a day (morning and night), and a third dose if necessary for a period of three weeks. Subjects will also have access to hyoscyamine as a rescue medication.
Placebo Suspension: The study is divided into three phases: 1 one-week baseline assessment followed by 2 three-week study phases (phase A and phase B). Phase A will require subjects to take 1/4 teaspoon placebo suspension 2 times a day (morning and night), and a third dose if necessary. In phase B subjects will not take the placebo. After 3 weeks in initial phase (either Phase A or B), subjects will switch to the alternate phase and continue the study for another 3 weeks. Hyoscyamine is available as a rescue medication during Phase A and Phase B. Half of the subjects will be randomized to begin with Phase A and half will be randomized to begin with Phase B.
Hyoscyamine: While not an intervention of interest to our study, patients will have hyoscyamine available as a rescue medication throughout the study. This can be taken on a PRN basis for breakthrough pain a maximum of 4x daily. | 15 |
| No Treatment First Followed by Placebo Arm 2: Subjects receive no treatment but have access to hyoscyamine as a rescue medication.
Hyoscyamine: While not an intervention of interest to our study, patients will have hyoscyamine available as a rescue medication throughout the study. This can be taken on a PRN basis for breakthrough pain a maximum of 4x daily. | 15 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | car accident | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo First Followed by no Treatment | No Treatment First Followed by Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 15 Participants | 30 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Functional abdominal pain | 15 Participants | 15 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 14 Participants | 27 Participants |
| Sex: Female, Male Female | 13 Participants | 12 Participants | 25 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 30 | 0 / 30 |
| other Total, other adverse events | 0 / 30 | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
The Primary Outcome Measure Was Mean Daily Pain
Change in mean pain score comparing both treatment arms to the baseline using the Visual analogue scale. (Scale 0-100mm) The scale reflects severity of the pain going from no pain (0) to maximum pain (100mm). Therefore the higher the number the more severe the pain is
Time frame: It will be assessed at the end of the 3-week and 6-week treatment periods (at the end of each treatment arm prior to crossover to the next arm of treatment)
Population: A total of 30 patients completed the study. All of them received placebo or no treatment in a randomized crossover study. All measurements during placebo are combined. All measurements during no treatment are combined. Statistcal models were adjusted for order of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | The Primary Outcome Measure Was Mean Daily Pain | 39.9 pain scale by VAS in mm | Standard Deviation 18 |
| No Treatment | The Primary Outcome Measure Was Mean Daily Pain | 45.14 pain scale by VAS in mm | Standard Deviation 14.7 |
p-value: <0.03ANCOVA
Secondary
Clinical Global Improvement
Compared clinical global improvement during each phase of the study The following question was used: Overall, how do you feel your problem is? (better, same, or worse). Patients were then divided in 2 groups: improved (if they answered better) vs not improved (if they answered same/worse)
Time frame: Following 1-week baseline and 3-week and 6-week treatment periods
Population: A total of 30 patients completed the study. All of them received placebo or no treatment in a randomized crossover study. All measurements during placebo are combined. All measurements during no treatment are combined. Statistical models were adjusted for order of treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Clinical Global Improvement | Improvement | 14 Participants |
| Placebo | Clinical Global Improvement | No improvement | 16 Participants |
| No Treatment | Clinical Global Improvement | Improvement | 9 Participants |
| No Treatment | Clinical Global Improvement | No improvement | 21 Participants |
p-value: 0.3McNemar
Secondary
Use of Rescue Medications
The number of medications used as rescue during each one of the periods of the study were counted
Time frame: 3 weeks of placebo vs 3 weeks of no treatment
Population: All patients
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Use of Rescue Medications | 2.0 pill count number | Standard Error 2.95 |
| No Treatment | Use of Rescue Medications | 3.8 pill count number | Standard Error 5.05 |
p-value: 0.001Wilcoxon (Mann-Whitney)