A Placebo-controlled Crossover Trial Using Cyproheptadine To Treat Children With Functional Abdominal Pain

Study Overview
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Brief Summary
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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

Official Title
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A Placebo-controlled Crossover Trial Using Cyproheptadine To Treat Children With Functional Abdominal Pain

Conditions
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Functional Abdominal Pain

Intervention / Treatment
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* Drug: Cyproheptadine
* Drug: sugar pill


Participation Criteria
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Eligibility Criteria
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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: Episodic or continuous abdominal pain Insufficient criteria for other FGIDs 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.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cyproheptadine first then Placebo<br>4 weeks of cyproheptadine or placebo with crossover to the other | Drug: Cyproheptadine<br>* 4 weeks of cyproheptadine or placebo with crossover to the other<br>* Other names: Periactin;Drug: sugar pill<br>* 4 weeks of cyproheptadine or placebo with crossover to the other<br>* Other names: placebo;|
| Experimental: Sugar Pill first then Cyprotheptadine<br>4 weeks of cyproheptadine or placebo with crossover to the other | Drug: Cyproheptadine<br>* 4 weeks of cyproheptadine or placebo with crossover to the other<br>* Other names: Periactin;Drug: sugar pill<br>* 4 weeks of cyproheptadine or placebo with crossover to the other<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | at 4 weeks of cyproheptadine or placebo treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 10 weeks |