ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12610000126011

Ethics application status

Approved

Date submitted

26/01/2010

Date registered

8/02/2010

Date last updated

8/02/2010

Type of registration

Prospectively registered

Titles & IDs

Public title

Efficacy of N-Alpha Methyl Histamine versus Propranolol in prevention of miigraine.

Scientific title

Efficacy of N alpha Methyl histamine versus propranolol in migraine prophylaxis

Secondary ID [1]

nil

Universal Trial Number (UTN)

U1111-1113-4606

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

migraine prophylaxis

Condition category

Condition code

Neurological

Other neurological disorders

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

a) Name of the treatment: N alpha methyl histamine in Evan’s solution (phenol 0.4%, isotonic sodium chloride) (10 ug/ml)
b) Dose administered 0.1 ml
c) Frequency and duration administered: twice a week for 12 weeks
d) Mode of administration: subcutaneous injection into back region of the upper arm.

The number of treatment/control arms in this trial.
Arm 1: N alpha methyl histamine + placebo propanolol
Arm 2: placebo N alpha methyl histamine + propanolol

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Patients randomized to receive oral propanolol will be given 40 mg/day for one week; then the dose will be increased 40 mg/week until a total daily dose of 120 mg/day which will be sustained for a period of twelve weeks. These patients will also receive subcutaneous placebo (Evan’s solution in back region of the upper arm) twice a week for a period of twelve weeks, administered in the same escalated-dose as N alpha methyl histamine.

Control group

Placebo

Outcomes

Primary outcome [1]

Significant decrease (with respect to basal values) in the magnitude of all parameters studied: assessed every month after randomisation (for 3 months).
1) Reduction in to rescue medication.
"Significant decrease" is a 20% reduction in the number of tablets ingested per month. This information will be recorded by the patient in the patient's diary.

Timepoint [1]

Recorded weekly for twelve weeks after randomisation.

Primary outcome [2]

Significant decrease (with respect to basal values) in the magnitude of
all parameters studied: assessed every month after randomisation (for 3 months)
2) Reduction in headache intensity (1-2-3). Recorded in the patient's diary.

Timepoint [2]

Recorded weekly for twelve weeks after randomisation.

Primary outcome [3]

Significant decrease (with respect to basal values) in the magnitude of
all parameters studied: assessed every month after randomisation (for 3 months)
3) Frequency of headache per month. Recorded by the patient in the patient's diary. Significant decrease is a 20% reduction in the number of attacks per month.

Timepoint [3]

Recorded weekly for twelve weeks after randomisation.

Secondary outcome [1]

Significant decrease (with respect to basal values) in the magnitude of all parameters studied: assessed every month after randomisation (for 3 months).
1) Duration of migraine attacks.
Recorded by the patient in the patient's diary. Significant decrease is a 20% reduction in the amount of hours each episode lasts. Measured in hours.

Timepoint [1]

Recorded weekly for twelve weeks after randomisation.

Eligibility

Key inclusion criteria

Inclusion Criteria.—The study will include outpatient male and female patients of any race between the ages of 18 and 65 years who have been diagnosed with migraine not attributable to another cause; with or without aura occurring for at least 15 consecutive days in a month, for 3 months in the absence of medication overuse. Migraine must have at least 2 of the following characteristics: unilateral location, pulsating quality, moderate or severe pain intensity, and/or aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs). With the following occurring during the attack: nausea and/or vomiting or photophobia and/or phonophobia.

Minimum age

18 Years

Maximum age

65 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Exclusion Criteria.—The following criteria are grounds for exclusion: female patients who are pregnant (positive urine pregnancy test) or planning to become pregnant during the study period, are breast feeding, or are of childbearing potential and not practicing a reliable method of birth control; patients with evidence of underlying conditions judged to preclude treatment with either test medication; patients who have previously used study medications for any reason; patients unable to discontinue any prohibited medication(s) including carbonic anhydrase inhibitors (eg, acetazolamide, dichlorphenamide), digoxin, metformin, central nervous system depressants (including alcohol), nonstudy anticonvulsant or antiepileptic medications, agents that might interfere with neuromuscular function (eg, aminoglycoside antibiotics, curare-like agents), or hormonal contraceptives; patients with evidence of recent alcohol/drug abuse or acute medication overuse; patients with diabetes mellitus, liver or kidney disease, recent (within 3 months) sepsis or vascular surgery, history of clinically significant pulmonary disease (eg, chronic obstructive pulmonary disease, asthma) active within the previous 12 months, history of heart attack or stroke, cardiac disorder (eg, any clinically significant dysrhythmia), aortic aneurysm, as well as patients at intermediate or higher risk for cardiac disease defined as having 2 or more major risk factors (cigarette smoking, hypotension).

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

Selected patients will undergo a one-month period of prophylactic agent washout, during which headache frequency will be monitored.

The method of allocation concealment was the use of sealed opaque envelopes.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Simple randomisation by using a randomisation table from a statistic book

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Parallel

Other design features

Phase

Phase 3

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

2/03/2010

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

Accrual to date

Final

Recruitment outside Australia

Country [1]

Mexico

State/province [1]

Colima

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

Hospital

Name

Hospital General deZona 1 Intituto Mexicano del Seguro Social

Address

Av. de los Maestros 149
Centro CP 28000
Colima, Colima

Country

Mexico

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Other collaborator category [1]

Individual

Name [1]

Saul Barreto Vizcaino

Address [1]

Instituto Mexicano del Seguro Social
Hospital General deZona1
Av. de los Maestros 149
Centro CP 28000
Colima, Colima

Country [1]

Mexico

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Comite de Etica del Hospital General de Zona 1 IMSS

Ethics committee address [1]

Hospital General de Zona 1 IMSS
No R-2007-601-9
 
Av. de los Maestros 149
Centro    CP28000
Colima, Colima

Ethics committee country [1]

Mexico

Date submitted for ethics approval [1]

01/05/2009

Approval date [1]

20/05/2009

Ethics approval number [1]

No R-2007-601-9

Summary

Brief summary

N alpha methyl histamine, possesses a greater affinity for H3 receptors, and could constitute a new therapeutic drug in migraine prophylaxis.
OBJETIVE. To compare the superior efficacy of the subcutaneous administration of N alpha-methyl histamine versus oral propranolol in migraine prophylaxis, undertaking double-blind, placebo-controlled study. 
Hypothesis
That subcutaneously injected N alpha methyl histamine (1-3ug) is more effective than propranolol (120mg/ day) in migraine prophylaxis.

Null Hypothesis  
There is no difference between the subcutaneous administration of N- alpha methyl histamine in doses of 1-3 ng and oral propanolol as prophylactic agents against migraine

METHODS. A randomized, double–blind study in 60 patients with migraine, male or female adults between the ages of 18 and 65 years. Selected patients will undergo a one-month period of prophylactic agent washout, they will then be divided into two groups for treatment in randomized blocks of three, double-blind fashion: N-alpha metyl histamine study group (n=30) and the propranolol control group (n=30). The treatment will consist of subcutaneous (back region of the upper arm) administration of N alpha methyl histamine twice a week, plus an oral placebo for a period of twelve weeks. Therapy with propranolol will begin at 40 mg/day for one week; until a total daily dose of 120 mg/day for a period of twelve weeks; plus a subcutaneous placebo. The variables we will study are: headache frequency; intensity of pain; duration of pain; intake of rescue analgesics and MIDAS. Statistical Analysis: The intent-to-treat (ITT) population will include all randomized patients. Two-tailed Student’s t test.  Mann-Whitney U rank sum test. In order to analyze the temporal course of each treatment, a Friedman repeated measures ANOVA on ranks test will be used to evaluate the statistical significance of differences between basal values and values found for the 4th, 8th, and 12th weeks of treatment. This study has been approved by the Ethical and Scientific Committee of our hospital.

Trial website

Trial related presentations / publications

1.Millan-Guerrero RO, Isais CM, Antonio OA, Pacheco-Carrasco MF. Histamine as a therapeutic alternative in   migraine prophylaxis: A randomized, placebo-controlled, double-blind study. Headache 1999;39:576-580

2.Millan-Guerrero RO, Pineda-Lucatero AG. Trujillo-Hernandez B, Tene CE, Pacheco MF. Na-Methyl histamine safety and efficacy in migraine prophylaxis: Phase I and Phase II study. Headache 2003;43:389-94

3.Millan-Guerrero RO, Isais- Millan R, Trujillo Hernandez B, Tene PC. . Na-Methyl Histamine safety and efficacy in migraine prophylaxis: Phase III study. Can J Neurol Sci 2006;33:195-199

4.Millan-Guerrero RO, Trujillo Hernandez B, Tene PC. Histamina subcutanea en profilaxis de migrana. Efectos iniciales y seguimiento a largo plazo. Neurologia 2006; 21:55-59  

5.Millan-Guerrero RO, Isais-Millan R, Barreto-Vizcaino S, Rivera-Castano L, Garcia-SA, Lopez BC, Membrila MM, Munoz SR. Subcutaneous histamine versus sodium valproate in migraine prophylaxis: A Randomized, Controlled, double-blind study. Eur J. Neurol.2007;14:1079-1084  

6.Millan-Guerrero RO, Isais-Millan S, Barreto-Vizcaino S, Rivera-Castano L, Rios-Madariaga C. Subcutaneous histamine versus botulinum toxin type A in migraine prophylaxis: a randomized, double-blind study. Eur J. Neurol  2009, 16: 88–94

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Contact person for public queries

Name

Dr. Rebeca Olivia Millan Guerrero

Address

Hospital General de Zona 1 IMSS
Avenida de los Maestros 149
Colonia Centro
CP 28000
Colima, Colima

Country

Mexico

Phone

01 52 31 23 14 17 57

Fax

01 52 31 23 14 17 57

rebeca.millan@imss.gob.mx

Contact person for scientific queries

Name

Dr. Rebeca Olivia Millan Guerrero

Address

Hospital General de Zona 1 IMSS
Avenida de los Maestros 149
Colonia Centro
CP 28000
Colima, Colima

Country

Mexico

Phone

0152 31 23 14 17 57

Fax

01 52 31 23 14 17 57

rebeca.millan@imss.gob.mx

No information has been provided regarding IPD availability

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

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