Diphenhydramine for Acute Migraine

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01825941
• Collaborator: (none)
• Enrollment: 208
• Location: 1
• Arms: 2
• Duration (Months): 20
• Patients Per Site Per Month: 10.4

Study Details

Study Description

Brief Summary

Parenteral diphenhydramine is commonly used as adjuvant therapy for acute migraine despite the fact that data supporting this practice do not exist. The investigators propose a randomized double blind study to test the hypothesis that 50mg of intravenous diphenhydramine, when added to standard migraine therapy, will result in a greater rate of sustained headache relief than standard migraine therapy alone. For this study, standard migraine therapy will be 10mg of intravenous metoclopramide. Sustained headache relief is defined as achieving a headache level of "mild" or "none" within two hours and maintaining a level of "mild" or "none" for 48 hours. Patients who present to the Montefiore emergency room (Bronx, NY) with an acute migraine will be approached for participation. They will be screened for medication contra-indications and non-migraine etiologies of headache. The study will be randomized. Assignment will be concealed. Participants and researchers will be blinded. Efficacy outcomes and adverse events will be assessed every half hour for two hours in the Emergency Department and by telephone 48 hours after medication administration. A sample size calculation, based on pilot data, revealed the need for 374 participants. An interim analysis will be performed after 200 participants have been enrolled with the goal of assessing for lack of conditional power.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Drug: metoclopramide; Drug: diphenhydramine; Drug: placebo	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 208 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Diphenhydramine as Adjuvant Therapy for Acute Migraine. A Randomized Trial.
• Study Start Date: Apr 1, 2013
• Actual Primary Completion Date: Dec 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Metoclopramide + Diphenhydramine Metoclopramide 10 milligrams + Diphenhydramine 50 milligrams, administered as an intravenous drip over 15 minutes	Drug: metoclopramide; 10 milligrams, administered intravenously over 15 minutes; Other Names: Reglan ; Drug: diphenhydramine; 50 milligrams, administered intravenously over 15 minutes; Other Names: Benadryl
Placebo Comparator: Metoclopramide + placebo Metoclopramide 10mg + placebo, administered intravenously over 15 minutes	Drug: metoclopramide; 10 milligrams, administered intravenously over 15 minutes; Other Names: Reglan ; Drug: placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Sustained Headache Relief Assessed by Self-evaluation [up to 2 hours in Emergency Department, 48 hours after discharge from Emergency Department]

   Sustained headache relief is defined as achieving a headache level of "mild" or "none" within two hours and maintaining a level of "mild" or "none" for 48 hours. Patient self-evaluated pain level is solicited every half hour for two hours in the Emergency Department and then by telephone 48 hours after discharge from emergency department

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Acute migraine headache

• Present to our emergency room in the Bronx, NY for treatment of migraine headache

Exclusion Criteria:

• Temperature > 100.3 F

• Pheochromocytoma

• Seizure disorder

• Parkinson's disease

• Use of monoamine oxidase (MAO) inhibitors

• Use of anti-rejection transplant medications

• Use of potassium supplements

• Use of pramlintide

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center	Bronx	New York	United States	10467

Sponsors and Collaborators

• Montefiore Medical Center

Investigators

• Principal Investigator: Benjamin W Friedman, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Benjamin W. Friedman, MD, Associate professor of Emergency Medicine, Montefiore Medical Center
• ClinicalTrials.gov Identifier: NCT01825941
• Other Study ID Numbers: 13-02-071
• First Posted: Apr 8, 2013
• Last Update Posted: Jul 31, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Benjamin W. Friedman, MD, Associate professor of Emergency Medicine, Montefiore Medical Center: migraine; headache; metoclopramide; diphenhydramine
• Additional relevant MeSH terms: Migraine Disorders; Diphenhydramine; Promethazine; Metoclopramide

Study Results

Participant Flow

Recruitment Details	Protocol anticipated enrollment of around 400 participants, however Data Safety Monitoring Board recommended enrollment cut to approximately half

Arm/Group Title	Metoclopramide + Diphenhydramine	Metoclopramide + Placebo
Arm/Group Description	Metoclopramide 10 milligrams + Diphenhydramine 50 milligrams, administered as an intravenous drip over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes diphenhydramine: 50 milligrams, administered intravenously over 15 minutes	Metoclopramide 10mg + placebo, administered intravenously over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes placebo
Period Title: Overall Study
STARTED	104	104
COMPLETED	100	103
NOT COMPLETED	4	1

Baseline Characteristics

Arm/Group Title	Metoclopramide + Diphenhydramine	Metoclopramide + Placebo	Total
Arm/Group Description	Metoclopramide 10 milligrams + Diphenhydramine 50 milligrams, administered as an intravenous drip over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes diphenhydramine: 50 milligrams, administered intravenously over 15 minutes	Metoclopramide 10mg + placebo, administered intravenously over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes placebo	Total of all reporting groups
Overall Participants	104	104	208
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (11)	36 (10)	35 (10)
Sex: Female, Male (Count of Participants)
Female	88 84.6%	92 88.5%	180 86.5%
Male	16 15.4%	12 11.5%	28 13.5%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (Count of Participants)
United States	104 100%	104 100%	208 100%
Duration of headache Prior to Study (Hours) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [Hours]	72	48	48

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Sustained Headache Relief Assessed by Self-evaluation
Description	Sustained headache relief is defined as achieving a headache level of "mild" or "none" within two hours and maintaining a level of "mild" or "none" for 48 hours. Patient self-evaluated pain level is solicited every half hour for two hours in the Emergency Department and then by telephone 48 hours after discharge from emergency department
Time Frame	up to 2 hours in Emergency Department, 48 hours after discharge from Emergency Department

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metoclopramide + Diphenhydramine	Metoclopramide + Placebo
Arm/Group Description	Metoclopramide 10 milligrams + Diphenhydramine 50 milligrams, administered as an intravenous drip over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes diphenhydramine: 50 milligrams, administered intravenously over 15 minutes	Metoclopramide 10mg + placebo, administered intravenously over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes placebo
Measure Participants	100	103
Count of Participants [Participants]	40 38.5%	38 36.5%

Adverse Events

Arm/Group Title	Metoclopramide + Diphenhydramine		Metoclopramide + Placebo
Arm/Group Description	Metoclopramide 10 milligrams + Diphenhydramine 50 milligrams, administered as an intravenous drip over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes diphenhydramine: 50 milligrams, administered intravenously over 15 minutes		Metoclopramide 10mg + placebo, administered intravenously over 15 minutes metoclopramide: 10 milligrams, administered intravenously over 15 minutes placebo
All Cause Mortality
	Metoclopramide + Diphenhydramine		Metoclopramide + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/104 (0%)
Serious Adverse Events
	Metoclopramide + Diphenhydramine		Metoclopramide + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/104 (0%)		0/103 (0%)
Other (Not Including Serious) Adverse Events
	Metoclopramide + Diphenhydramine		Metoclopramide + Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/104 (24%)		21/104 (20.2%)
Nervous system disorders
Restlessness	8/104 (7.7%)	8	7/104 (6.7%)	7
Drowsy	17/104 (16.3%)	17	14/104 (13.5%)	14

Limitations/Caveats

[Not Specified]

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.