Melatonin in Pediatric FD Population
Condition: Dyspepsia
MeSH terms: Dyspepsia
Study type: Interventional

Summary: 
      There are two specific aims in this study.

      Specific Aim 1: Determine if melatonin results in a higher grade of clinical response than
      does placebo in children with functional dyspepsia (FD).

      Hypothesis: treatment of FD with melatonin will result in a higher grade of clinical response
      than will treatment with a placebo.

      Specific Aim 2: Evaluate the relationship between changes in sleep and improvement in pain in
      pediatric patients with functional dyspepsia receiving melatonin.

      Hypothesis: There will be no association between improvement in pain and improvement in sleep
      in children with functional dyspepsia receiving melatonin.
    

Detailed description: 
      Recurrent abdominal pain is present in a significant proportion of the pediatric population
      at large. Often times, no clear organic cause for pain will be found, and these children are
      diagnosed with functional abdominal pain. Of the children with functional abdominal pain,
      many are classified as having functional dyspepsia (FD). Functional dyspepsia is defined as
      persistent or recurrent pain or discomfort centered in the upper abdomen (above the
      umbilicus) that is unrelated to a change in stool frequency or form and not exclusively
      relieved by defecation. There have been only a few placebo controlled trials of medications
      in children with abdominal pain and none in children specifically with functional dyspepsia
      and uninvestigated mucosal inflammation.

      There is increasing evidence suggesting that melatonin plays a role in pain modulation.
      Melatonin is produced by the pineal gland and is recognized for its regulation of sleep and
      circadian functions. Less widely recognized is melatonin's production in other parts of the
      body; such as in the digestive system and in immune cells including mast cells. The total
      amount of melatonin in the digestive system exceeds that of the pineal gland and blood.
      Within the digestive tract, melatonin is produced in the enterochromaffin cells. It exerts
      both excitatory and inhibitory effects on the enteric nervous system as well as possessing
      anti-inflammatory and immunomodulatory properties. In a rat model of reflux esophagitis,
      melatonin demonstrated multiple effects on the esophageal mucosa. These included decreased
      lipid peroxidation (oxidative degradation of lipids in cell membranes which leads to cell
      damage), replenished superoxide dismutase and glutathione (improved defense of the mucosa),
      and decreased expression of T helper 1 cytokines (pro-inflammatory cytokines) while not
      altering anti inflammatory cytokines. These effects may account for the reduction in pain in
      adults with irritable bowel syndrome (IBS) and dyspepsia during a trial of melatonin therapy.
      In a study of adults with IBS in association with sleep disturbances, patients were given
      melatonin 3mg or placebo at bedtime for two weeks. Compared with the placebo group, the group
      who received melatonin had significantly lower mean abdominal pain scores while sleep
      parameters were not influenced. In a study of adults with functional dyspepsia, twelve weeks
      of melatonin (5 mg taken at bedtime) resulted in 56.6% of patients having complete resolution
      of symptoms and 30% having partial improvement, while only 6.7% of the patients who received
      placebo experienced any improvement in symptoms. Melatonin has not been previously studied in
      children with abdominal pain. Evaluation of its effects is warranted as melatonin would be a
      very safe and inexpensive alternative treatment.
    

Intervention name(s): Melatonin; Placebo
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Comparison between melatonin and placebo (2 weeks each) with active and placebo crossover during the study period of 34-36 days.
Other intervention name(s): Melatonin 5 mg.
Intervention MeSH terms: Melatonin
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Functional Dyspepsia; Melatonin; Pain; Actigraphy and Pain