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

• Sponsor: University of Michigan (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01675050
• Collaborator: (none)
• Enrollment: 4
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Functional Abdominal Pain	Drug: Cyproheptadine; Drug: sugar pill	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 4 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Placebo-controlled Crossover Trial Using Cyproheptadine To Treat Children With Functional Abdominal Pain
• Study Start Date: Aug 1, 2012
• Actual Primary Completion Date: Aug 1, 2013
• Actual Study Completion Date: Aug 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cyproheptadine first then Placebo 4 weeks of cyproheptadine or placebo with crossover to the other	Drug: Cyproheptadine; 4 weeks of cyproheptadine or placebo with crossover to the other; Other Names: Periactin ; Drug: sugar pill; 4 weeks of cyproheptadine or placebo with crossover to the other; Other Names: placebo
Experimental: Sugar Pill first then Cyprotheptadine 4 weeks of cyproheptadine or placebo with crossover to the other	Drug: Cyproheptadine; 4 weeks of cyproheptadine or placebo with crossover to the other; Other Names: Periactin ; Drug: sugar pill; 4 weeks of cyproheptadine or placebo with crossover to the other; Other Names: placebo

Outcome Measures

Primary Outcome Measures

1. 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

1. 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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UmichiganHS	Ann Arbor	Michigan	United States	48105

Sponsors and Collaborators

• University of Michigan

Investigators

• Principal Investigator: Ismaeel Hashemi, MD, University of Michigan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ismaeel Hashemi, Fellow Physician, University of Michigan
• ClinicalTrials.gov Identifier: NCT01675050
• Other Study ID Numbers: HUM00056045
• First Posted: Aug 29, 2012
• Last Update Posted: Aug 30, 2017
• Last Verified: Aug 1, 2017

• Additional relevant MeSH terms: Abdominal Pain; Cyproheptadine

Study Results

Participant Flow

Arm/Group Title	Cyproheptadine First, Then Placebo	Sugar Pill First, Than Cyproheptadine
Arm/Group Description	4 weeks of cyproheptadine with crossover to 4 weeks of placebo.	4 weeks of placebo (sugar pill) with crossover to 4 weeks of cyproheptadine
Period Title: Period One Treatment
STARTED	2	2
COMPLETED	1	2
NOT COMPLETED	1	0
Period Title: Period One Treatment
STARTED	1	2
COMPLETED	1	2
NOT COMPLETED	0	0
Period Title: Period One Treatment
STARTED	1	2
COMPLETED	1	2
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Cyproheptadine Then Placebo	Placebo Then Cyproheptadine	Total
Arm/Group Description	4 weeks of cyproheptadine with crossover to 4 weeks of placebo.	4 weeks of placebo (sugar pill) with crossover to 4 weeks of cyproheptadine	Total of all reporting groups
Overall Participants	2	2	4
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	12.5	10.5	11.5
Sex: Female, Male (Count of Participants)
Female	1 50%	2 100%	3 75%
Male	1 50%	0 0%	1 25%
Region of Enrollment (Count of Participants)
United States	2 100%	2 100%	4 100%
Pressure Pain Threshold (kg/cm^2) [Mean (Standard Deviation) ]
Baseline prior to First Treatment	1.75 (2)	1.28 (.53)	1.51 (.99)
Baseline prior to Second Treatment	1.25 (0)	1.08 (.18)	1.13 (.16)
Improvement in Abdominal Pain (units on a scale) [Mean (Standard Deviation) ]
Baseline prior to First Treatment	4 (5.66)	8.5 (2.12)	6.25 (4.35)
Baseline prior to Second Treatment	6 (0)	6.5 (3.45)	6.33 (2.52)

Outcome Measures

1. Primary Outcome

Title	Pressure Pain Threshold
Description	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.
Time Frame	at 4 weeks of cyproheptadine or placebo treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants Post Cyproheptadine	All Participants Post Placebo
Arm/Group Description
Measure Participants	4	3
Mean (Standard Deviation) [kg/cm^2]	1.15 (.73)	1.23 (.39)

2. Secondary Outcome

Title	Abdominal Pain
Description	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).
Time Frame	10 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	All Participants Post Cyproheptadine	All Participants Post Placebo
Arm/Group Description
Measure Participants	4	3
Mean (Standard Deviation) [units on a scale]	5.25 (4.11)	8 (2)

Adverse Events

Time Frame	10 weeks during study
Arm/Group Title	Cyproheptadine		Placebo
Arm/Group Description	All participants while on Cyproheptadine.		All participants while on Placebo.
All Cause Mortality
	Cyproheptadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Cyproheptadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Cyproheptadine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/4 (75%)		1/3 (33.3%)
General disorders
Increase Appetite	1/4 (25%)		1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Weakness	1/4 (25%)		0/3 (0%)
Nervous system disorders
Somnolence (Drowsiness)	2/4 (50%)		1/3 (33.3%)
Dizziness	1/4 (25%)		0/3 (0%)
Psychiatric disorders
Restless Sleeping Pattern	1/4 (25%)		0/3 (0%)
Trouble Sleeping (Insomnia)	1/4 (25%)		0/3 (0%)
Vascular disorders
Cold Sweats	1/4 (25%)		0/3 (0%)

Limitations/Caveats

Statistical analyses were not conducted due to small sample size. Results should be interpreted with extreme caution.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.