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

Phase 2

Terminated

Conditions: Functional Abdominal Pain

Interventions: Drug: Cyproheptadine
Drug: sugar pill

Registration Number: NCT01675050

Lead Sponsor: University of Michigan

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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 4

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Cyproheptadine first then Placebo	Cyproheptadine	4 weeks of cyproheptadine or placebo with crossover to the other
Cyproheptadine first then Placebo	sugar pill	4 weeks of cyproheptadine or placebo with crossover to the other
Sugar Pill first then Cyprotheptadine	sugar pill	4 weeks of cyproheptadine or placebo with crossover to the other
Sugar Pill first then Cyprotheptadine	Cyproheptadine	4 weeks of cyproheptadine or placebo with crossover to the other

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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).