Functional Abdominal Pain
Conditions
Brief summary
The investigators hypothesize that using Cyproheptadine in a placebo-controlled crossover trial would help relieve abdominal pain associated with (Functional Abdominal Pain (FAP) in children, achieving a greater response than that observed with placebo. In addition to assessing self-report of pain and other symptoms, the investigators also propose to perform experimental somatic pain testing to determine if there is evidence of peripherally-maintained central sensitization in children with FAP. The investigators also hypothesize that there will be an increase in somatic pain threshold after completion of a Cyproheptadine course compared to baseline testing prior to treatment, and compared to placebo. This would allow children with FAP to return to normal function, improve symptoms and overall general well-being
Interventions
DRUGCyproheptadine
4 weeks of cyproheptadine or placebo with crossover to the other
DRUGsugar pill
4 weeks of cyproheptadine or placebo with crossover to the other
Sponsors
University of Michigan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
8 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Age between 8 and 18 years-old * Diagnosed with Functional Abdominal Pain using the Rome III Criteria must include all\* of the following: 1. Episodic or continuous abdominal pain 2. Insufficient criteria for other FGIDs 3. No evidence of an inflammatory, anatomic, metabolic, or neoplastic process that explains the subject's symptoms * Criteria fulfilled at least once per week for at least 2 months prior to diagnosis * Written informed consent obtained from the patient/guardian before the initiation of any study-specific procedures
Exclusion criteria
* Age \< 8 years-old or Age \>18 years-old * Child or parent are non-English speakers * Child is using other CNS depressants (cyproheptadine causes drowsiness, and may enhance the adverse/toxic effect of other CNS Depressants e.g. opioids, barbiturates, Droperidol, Hydroxyzine, Alcohol)(29) * Child has a history of hypersensitivity to Cyproheptadine products * Child is currently using monoamine oxidase inhibitor (MAOI e.g. Nardil, Marplan, Parnate) (can cause a prolonged or intensified anticholinergic effect) * Child was treated with Cyproheptadine in the past 4 weeks * Child is currently using anticholinergic (can cause an additive anticholinergic effect e.g. Pramlintide) * Concomitant SSRI use ( being a serotonin antagonist, may oppose effects) * Concomitant use of Betahistine: Antihistamines may diminish the therapeutic effect of Betahistine * Concomitant use of Acetylcholinesterase Inhibitors (Central): Anticholinergics may diminish the therapeutic effect of Acetylcholinesterase Inhibitors (Central) and vice versa. * Child has a personal history of glaucoma * Child has asthma (can cause thickening of bronchial secretions) (27,28) * History of liver dysfunction/disease (can cause hepatitis) * History of cardiac disease (not specific to Cyproheptadine, antihistamines have been associated with hypotension, palpitations, tachycardia and arrhythmias) (28,29). * Females who are known to be pregnant will also be excluded. All females who are of child bearing age, or are already menstruating will perform a urine pregnancy test before enrolling. * Any children who have difficulties swallowing tablets will receive teaching on how to swallow tablets. If they are still unable to do so, they will not participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pressure Pain Threshold | at 4 weeks of cyproheptadine or placebo treatment | Increasing pressures were applied with a pressure plunger to the participants' thumbnail. The pressure at which the participant said that s/he felt pain is noted. The pressure is measured in kilograms by centimeters squared. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Abdominal Pain | 10 weeks | Participants rated the highest intensity of abdominal pain they experienced during the past two weeks on a scale of 0 (No Pain) to 10 (The Most Pain Possible), as derived from the Abdominal Pain Index - Child Version (Laird et al. 2015. Journal of Pediatric Psychology, 40(5), 517-525). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cyproheptadine Then Placebo 4 weeks of cyproheptadine with crossover to 4 weeks of placebo. | 2 |
| Placebo Then Cyproheptadine 4 weeks of placebo (sugar pill) with crossover to 4 weeks of cyproheptadine | 2 |
| Total | 4 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period One Treatment | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Then Cyproheptadine | Total | Cyproheptadine Then Placebo |
|---|---|---|---|
| Age, Continuous | 10.5 years | 11.5 years | 12.5 years |
| Improvement in Abdominal Pain Baseline prior to First Treatment | 8.5 units on a scale STANDARD_DEVIATION 2.12 | 6.25 units on a scale STANDARD_DEVIATION 4.35 | 4 units on a scale STANDARD_DEVIATION 5.66 |
| Improvement in Abdominal Pain Baseline prior to Second Treatment | 6.5 units on a scale STANDARD_DEVIATION 3.45 | 6.33 units on a scale STANDARD_DEVIATION 2.52 | 6 units on a scale STANDARD_DEVIATION 0 |
| Pressure Pain Threshold Baseline prior to First Treatment | 1.28 kg/cm^2 STANDARD_DEVIATION 0.53 | 1.51 kg/cm^2 STANDARD_DEVIATION 0.99 | 1.75 kg/cm^2 STANDARD_DEVIATION 2 |
| Pressure Pain Threshold Baseline prior to Second Treatment | 1.08 kg/cm^2 STANDARD_DEVIATION 0.18 | 1.13 kg/cm^2 STANDARD_DEVIATION 0.16 | 1.25 kg/cm^2 STANDARD_DEVIATION 0 |
| Region of Enrollment United States | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Female | 2 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 4 | 1 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
Pressure Pain Threshold
Increasing pressures were applied with a pressure plunger to the participants' thumbnail. The pressure at which the participant said that s/he felt pain is noted. The pressure is measured in kilograms by centimeters squared.
Time frame: at 4 weeks of cyproheptadine or placebo treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants Post Cyproheptadine | Pressure Pain Threshold | 1.15 kg/cm^2 | Standard Deviation 0.73 |
| All Participants Post Placebo | Pressure Pain Threshold | 1.23 kg/cm^2 | Standard Deviation 0.39 |
Secondary
Abdominal Pain
Participants rated the highest intensity of abdominal pain they experienced during the past two weeks on a scale of 0 (No Pain) to 10 (The Most Pain Possible), as derived from the Abdominal Pain Index - Child Version (Laird et al. 2015. Journal of Pediatric Psychology, 40(5), 517-525).
Time frame: 10 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| All Participants Post Cyproheptadine | Abdominal Pain | 5.25 units on a scale | Standard Deviation 4.11 |
| All Participants Post Placebo | Abdominal Pain | 8 units on a scale | Standard Deviation 2 |