A Placebo-controlled Crossover Trial Using Cyproheptadine To Treat Children With Functional Abdominal Pain
Condition: Functional Abdominal Pain
MeSH terms: Abdominal Pain
Intervention: Cyproheptadine; sugar pill
Intervention description: 4 weeks of cyproheptadine or placebo with crossover to the other; 4 weeks of cyproheptadine or placebo with crossover to the other
Intervention MeSH terms: Cyproheptadine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 4.0
Sex: All
Minimum age: 8 Years
Maximum age: 18 Years
Healthy volunteers: No

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
    

Eligibility criteria:

        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.