DyspepsiaNCT04684199
Melatonin in Pediatric FD Population
A study testing Melatonin in people with Dyspepsia, run by Children's Mercy Hospital Kansas City at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 8 to 17 years
- Conditions the study is for
- Dyspepsia
- What is being tested?
- Melatonin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2014to Apr 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 8 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Patients seen in the GI clinic with a diagnosis of functional dyspepsia as defined by Rome III criteria.
- Persistent pain despite acid suppression at therapeutic doses for at least 4 weeks
- Patients ages 8-17 years, inclusive.
Who cannot join
- Patients currently using melatonin.
- Patients who have previously had endoscopy.
- Initiation of a treatment plan that includes one or more of the following medications in the last 4 weeks
- Opiates
- Tramadol
- Gabapentin
- Benzodiazepines
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Therapeutic Effect of Melatonin in Pediatric Patients With Functional Dyspepsia
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.
Read the 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MelatoninDietary supplement
Also called Melatonin 5 mg.
Comparison between melatonin and placebo (2 weeks each) with active and placebo crossover during the study period of 34-36 days.
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Active comparator | Melatonin
All participants will receive a 5 mg. dose of melatonin before bed for a period of two weeks during study period. Receives: Dietary Supplement: Melatonin |
| Placebo | Placebo comparator | Placebo
All participants will receive a placebo comparative in substance, color, and flavor, before bed for two weeks during the study. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Grade of clinical response to Melatonin in children with functional dyspepsia
The overall positive response rate (grade 3-5) will be compared between melatonin and placebo by the McNemar test.
Measured: 35 days
Secondary outcomes (1)
Change in sleep in pediatric patients with functional dyspepsia receiving melatonin
The mean sleep latency and mean sleep duration from sleep diary and actigraphy data will be compared between baseline and therapy for melatonin and placebo, respectively, using the paired Student's t test.
Measured: 35 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2020
- Study startAug 2014
- Primary completionApr 2015
- Study completionApr 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for DyspepsiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Mercy Hospital Kansas City
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Katherine Sturgeon, MD, Principal investigator, Children's Mercy Hospital Kansas City
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04684199
- Sponsor's protocol ID
- 14010042
- Status last verified
- Dec 2020
- First submitted
- 23 Jul 2014
- Last updated
- 24 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
APLEY J, NAISH N. Recurrent abdominal pains: a field survey of 1,000 school children. Arch Dis Child. 1958 Apr;33(168):165-70. doi: 10.1136/adc.33.168.165. No abstract available.
PubMed 13534750Rasquin-Weber A, Hyman PE, Cucchiara S, Fleisher DR, Hyams JS, Milla PJ, Staiano A. Childhood functional gastrointestinal disorders. Gut. 1999 Sep;45 Suppl 2(Suppl 2):II60-8. doi: 10.1136/gut.45.2008.ii60.
PubMed 10457047Shaffer SE, Sellman SB, Repucci AH, Hupertz VF, Czinn SJ, Boyle JT. Dyspepsia: Redefining chronic abdominal pain in children. Gastroenterology. 1992; 102:163A
Ambriz-Tututi M, Rocha-Gonzalez HI, Cruz SL, Granados-Soto V. Melatonin: a hormone that modulates pain. Life Sci. 2009 Apr 10;84(15-16):489-98. doi: 10.1016/j.lfs.2009.01.024. Epub 2009 Feb 15.
PubMed 19223003Maldonado MD, Mora-Santos M, Naji L, Carrascosa-Salmoral MP, Naranjo MC, Calvo JR. Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation. Pharmacol Res. 2010 Sep;62(3):282-7. doi: 10.1016/j.phrs.2009.11.014. Epub 2009 Dec 4.
PubMed 19963060Klupinska G, Poplawski T, Drzewoski J, Harasiuk A, Reiter RJ, Blasiak J, Chojnacki J. Therapeutic effect of melatonin in patients with functional dyspepsia. J Clin Gastroenterol. 2007 Mar;41(3):270-4. doi: 10.1097/MCG.0b013e318031457a.
PubMed 17426465Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005 Oct;54(10):1402-7. doi: 10.1136/gut.2004.062034. Epub 2005 May 24.
PubMed 15914575Lahiri S, Singh P, Singh S, Rasheed N, Palit G, Pant KK. Melatonin protects against experimental reflux esophagitis. J Pineal Res. 2009 Mar;46(2):207-13. doi: 10.1111/j.1600-079X.2008.00650.x. Epub 2008 Nov 28.
PubMed 19067786Buck M. The Use of Melatonin in Children With Sleep Disturbances. Pediatr Pharm. 2003;9(11)
Kobayashi I, Hall B, Palmieri P. Acigraphy improves measurements of sleep functioning. Traumatic Stress Points. 2008 Mar Vol 22, Issue 2
Meltzer LJ, Montgomery-Downs HE, Insana SP, Walsh CM. Use of actigraphy for assessment in pediatric sleep research. Sleep Med Rev. 2012 Oct;16(5):463-75. doi: 10.1016/j.smrv.2011.10.002. Epub 2012 Mar 15.
PubMed 22424706Cellini N, Buman MP, McDevitt EA, Ricker AA, Mednick SC. Direct comparison of two actigraphy devices with polysomnographically recorded naps in healthy young adults. Chronobiol Int. 2013 Jun;30(5):691-8. doi: 10.3109/07420528.2013.782312. Epub 2013 May 30.
PubMed 23721120Sadeh A, Sharkey KM, Carskadon MA. Activity-based sleep-wake identification: an empirical test of methodological issues. Sleep. 1994 Apr;17(3):201-7. doi: 10.1093/sleep/17.3.201.
PubMed 7939118Weiss MD, Wasdell MB, Bomben MM, Rea KJ, Freeman RD. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry. 2006 May;45(5):512-519.
PubMed 16670647
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Therapeutic Effect of Melatonin in Pediatric Patients With Functional Dyspepsia
- ClinicalTrials.gov ID
- NCT04684199
- Acronym / sponsor ID
- 14010042
- Conditions
- Dyspepsia
- Keywords
- Functional Dyspepsia, Melatonin, Pain, Actigraphy and Pain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Children's Mercy Hospital Kansas CityUniversity, hospital or other
- Study start
- Aug 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 24 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Active comparator | Dietary Supplement: MelatoninMelatonin All participants will receive a 5 mg. dose of melatonin before bed for a period of two weeks during study period. |
| Placebo | Placebo comparator | Dietary Supplement: PlaceboPlacebo All participants will receive a placebo comparative in substance, color, and flavor, before bed for two weeks during the study. |
Who may qualify
- Ages
- 8 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- Patients seen in the GI clinic with a diagnosis of functional dyspepsia as defined by Rome III criteria.
- Persistent pain despite acid suppression at therapeutic doses for at least 4 weeks
- Patients ages 8-17 years, inclusive.
Key exclusion criteria (7 listed)
- Patients currently using melatonin.
- Patients who have previously had endoscopy.
- Initiation of a treatment plan that includes one or more of the following medications in the last 4 weeks
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MelatoninAlso: Melatonin 5 mg.Comparison between melatonin and placebo (2 weeks each) with active and placebo crossover during the study period of 34-36 days. | Dietary supplement | Melatonin |
| Placebo | Dietary supplement | Placebo |
Primary outcome
Grade of clinical response to Melatonin in children with functional dyspepsia
Time frame: 35 days
The overall positive response rate (grade 3-5) will be compared between melatonin and placebo by the McNemar test.
1 secondary outcome
Change in sleep in pediatric patients with functional dyspepsia receiving melatonin
Time frame: 35 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2020.
- Background: PubMed 13534750APLEY J, NAISH N. Recurrent abdominal pains: a field survey of 1,000 school children. Arch Dis Child. 1958 Apr;33(168):165-70. doi: 10.1136/adc.33.168.165. No abstract available.
- Background: PubMed 10457047Rasquin-Weber A, Hyman PE, Cucchiara S, Fleisher DR, Hyams JS, Milla PJ, Staiano A. Childhood functional gastrointestinal disorders. Gut. 1999 Sep;45 Suppl 2(Suppl 2):II60-8. doi: 10.1136/gut.45.2008.ii60.
- BackgroundShaffer SE, Sellman SB, Repucci AH, Hupertz VF, Czinn SJ, Boyle JT. Dyspepsia: Redefining chronic abdominal pain in children. Gastroenterology. 1992; 102:163A
- Background: PubMed 19223003Ambriz-Tututi M, Rocha-Gonzalez HI, Cruz SL, Granados-Soto V. Melatonin: a hormone that modulates pain. Life Sci. 2009 Apr 10;84(15-16):489-98. doi: 10.1016/j.lfs.2009.01.024. Epub 2009 Feb 15.
- Background: PubMed 19963060Maldonado MD, Mora-Santos M, Naji L, Carrascosa-Salmoral MP, Naranjo MC, Calvo JR. Evidence of melatonin synthesis and release by mast cells. Possible modulatory role on inflammation. Pharmacol Res. 2010 Sep;62(3):282-7. doi: 10.1016/j.phrs.2009.11.014. Epub 2009 Dec 4.
- Background: PubMed 17426465Klupinska G, Poplawski T, Drzewoski J, Harasiuk A, Reiter RJ, Blasiak J, Chojnacki J. Therapeutic effect of melatonin in patients with functional dyspepsia. J Clin Gastroenterol. 2007 Mar;41(3):270-4. doi: 10.1097/MCG.0b013e318031457a.
- Background: PubMed 15914575Song GH, Leng PH, Gwee KA, Moochhala SM, Ho KY. Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut. 2005 Oct;54(10):1402-7. doi: 10.1136/gut.2004.062034. Epub 2005 May 24.
- Background: PubMed 19067786Lahiri S, Singh P, Singh S, Rasheed N, Palit G, Pant KK. Melatonin protects against experimental reflux esophagitis. J Pineal Res. 2009 Mar;46(2):207-13. doi: 10.1111/j.1600-079X.2008.00650.x. Epub 2008 Nov 28.
- BackgroundBuck M. The Use of Melatonin in Children With Sleep Disturbances. Pediatr Pharm. 2003;9(11)
- BackgroundKobayashi I, Hall B, Palmieri P. Acigraphy improves measurements of sleep functioning. Traumatic Stress Points. 2008 Mar Vol 22, Issue 2
- Background: PubMed 22424706Meltzer LJ, Montgomery-Downs HE, Insana SP, Walsh CM. Use of actigraphy for assessment in pediatric sleep research. Sleep Med Rev. 2012 Oct;16(5):463-75. doi: 10.1016/j.smrv.2011.10.002. Epub 2012 Mar 15.
- Background: PubMed 23721120Cellini N, Buman MP, McDevitt EA, Ricker AA, Mednick SC. Direct comparison of two actigraphy devices with polysomnographically recorded naps in healthy young adults. Chronobiol Int. 2013 Jun;30(5):691-8. doi: 10.3109/07420528.2013.782312. Epub 2013 May 30.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine Sturgeon, MD principal investigator
Children's Mercy Hospital Kansas City
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Melatonin in people with Dyspepsia, run by Children's Mercy Hospital Kansas City at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Grade of clinical response to Melatonin in children with functional dyspepsia (time frame: 35 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04684199, which also lists 14 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2020.