Efficacy of Individualized Homeopathic Remedies on Migraine: a Randomized, Triple-blind, Placebo Controlled Study.

Study Overview
=================
Brief Summary
-----------------
Migraine, a chronic and often lifelong neurological disorder, is the second leading cause of years lived with disability worldwide. To reduce this global burden, concerted efforts are needed to implement and improve migraine health-care policies. Several observational studies showed significant improvement of different headaches types with homeopathy. The purpose of this study is the assessment of the efficacy of Individualized Homeopathic Remedies (specific remedies for each patient) versus Conventional pharmacological treatment in patients with migraine.

Detailed Description
-----------------
This is a randomized, triple-blind, placebo-controlled, parallel group study in adult subjects with diagnosis of migraine with or without aura. All patients will be assessed in a screening visit at the Study Hospital Dept. of Neurology in order to confirm and certify migraine diagnosis and evaluate correctness and stability of usual acute and preventive standardized pharmacological treatment. Patients will fulfill a 30 day baseline period to monitor headache activity, migraine related symptoms, and medication usage. Subjects agreeing to participate in the study and meeting clinical-neurological eligibility criteria will then assist to a first homeopathic consultation to assess viability of homeopathic treatment and selection of the individualized homeopathic remedy. Patients who meet both neurological and homeopathic inclusion criteria will begin a three month treatment phase. An estimated of 72 patients, calculated according to the Open-Epi program ((c) 2003, 2008 Andrew G. Dean and Kevin M. Sullivan, Atlanta, GA, USA) , will be randomized according to statistics Epidat Program (4.2 version, july 2016 Panamerican Health Organization (PHO-WHO); to receive Individualized homeopathic treatment + standard pharmacological treatment OR unidentified placebo + standard pharmacological treatment. Study homeopathic remedy or placebo will be administered for a minimum period of 12 weeks with control visits every 4 weeks to assess neurological and homeopathic evolution, adherence and possible adverse events. During the study period patients will continue filling the migraine diary collecting frequency, length and type of headaches, acute medication usage and migraine associated symptoms. At the end of treatment, a final clinical homeopathic visit will take place as well as a final Neurological visit at study Hospital. Hospital visits are independent of clinical visits and performed by different study physicians. After conclusion of treatment phase patients will have three more follow up visits for the assessment of clinical and homeopathic evolution, possible adverse events and general satisfaction with the study.

Official Title
-----------------
Randomized, Triple-blind, Placebo Controlled Study to Evaluate the Efficacy of Individualized Homeopathic Remedies With High Grade of Pathological Similarity vs Conventional Standardized Pharmacological Treatment in Patients With Migraine.

Conditions
-----------------
Migraine

Intervention / Treatment
-----------------
* Other: Individualized Homeopathic Remedy
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with certified diagnosis of migraine with or with out aura of at least one year of evolution according to the Subcommittee of Headaches Classification of the International Headache Association 3rd edition (ICHD-III) Patients receiving acute or preventive standardized pharmacological treatment for migraine for at least one year prior to study inclusion Patients do not have chronic migraine defined as Headache occurring on 15 or more days per month for more than 3 months, which has the features of migraine headache on at least 8 days per month (ICHD-III) Patients meeting ICHD-III criteria of probable medication overuse headache (MOH) Female patients in reproductive age that are correctly using a standardized contraceptive method Participants who are able to maintain a prospectively collected simple headache diary Exclusion Criteria: Patients under standardized pharmacological treatment who have significantly (>50%) added or modified migraine preventive drugs doses within 3 months prior to study baseline Patients who have initiated or significantly (>50%) modified doses of any drug for any chronic treatment with any agent with proven analgesic action or psychiatric action (antidepressants, antipsychotics, mood stabilizers, etc) or neurological action (anticonvulsivants, antiparkinsonians, etc) within 3 months prior to study baseline Patients suffering any cause of secondary headache like trauma, metabolic or vascular disorders, non vascular intracranial lesions, abuse of alcohol or other psychoactive substances. Pregnant or probably pregnant patients according to date of last menstruation referred by the patient of more than 35 days in women with regular cycles or plasma beta sub-unit of human chorionic gonadotrophin in women with irregular menstrual cycles Patients with history of anaphylaxis, non controlled diabetes, severe disorders being neurological, cardiac, pulmonary and/or hepatic as well as psychosis or suicide ideation and/or attempts. Patients with other acute or chronic pain disorders, history of hemiplegic migraine or migraine with brain stem aura, history of cerebral-vascular accident, convulsions, severe coronary disease, non controlled hypertension or cognitive dysfunctions. Patients not meeting homeopathic clinical criteria of High Pathological Similitude defined as an homeopathic previous success probability for the selected homeopathic remedy of of 5 to 7 points in a probability scale of 1 to 7 NOTE: Please contact the investigator for additional information about Homeopathic criteria

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized, Triple-blind, Placebo Controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Individualized Homeopathic Remedy plus Standard Pharmacologic Treatment<br>Each subject receives an individually selected homeopathic remedy (individualized homeopathic remedy) as an add on to the conventional standardized pharmacological treatment he/she is receiving prior and during study. Standardized pharmacological treatment will be monitored and approved at first hospital neurological visit and as a requirement needs to be unchanged within 3 months prior inclusion and throughout the study. | Other: Individualized Homeopathic Remedy<br>* An individualized homeopathic remedy selected for each subject according clinical homeopathic parameters will be administered daily in the form of oral globules as an add on to conventional treatment.<br>|
| Placebo Comparator: Placebo plus Standard Pharmacologic Treatment<br>Subjects receive an indistinguishable placebo plus the conventional standardized pharmacological treatment he/she is receiving prior and during study. Standardized pharmacological treatment will be monitored and approved at first hospital neurological visit and as a requirement needs to be unchanged within 3 months prior inclusion and throughout the study. | Other: Placebo<br>* Placebo plus Standard Pharmacologic Treatment<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of migraine attacks | Assess the efficacy of chosen individualized homeopathic remedy in the preventive treatment of migraine, measuring the change in the number of weekly migraine attacks comparing baseline to the final month of the 3-month treatment period versus placebo. | Baseline - Month 3 | 
| Number of migraine days | Assess the efficacy of chosen individualized homeopathic remedy in the preventive treatment of migraine, measuring the change in the number of monthly migraine days comparing baseline to the final month of the 3-month treatment period versus placebo. | Baseline - Month 3 | 
| Responder in frequency of migraine attacks | Number of subjects achieving diminution in more than 50% of migraine attacks per month comparing baseline to the final month of the 3-month treatment period versus placebo | Baseline - Month 3 | 
| Responder in quantity of migraine days | Number of subjects achieving diminution in more than 50% of migraine days per month comparing baseline to the final month of the 3-month treatment period versus placebo | Baseline - Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Migraine acute medication usage doses | Assess the efficacy of chosen individualized homeopathic remedy in the preventive treatment of migraine, measured by the change of the required doses of standard pharmacological acute migraine drugs comparing baseline to the final month of the 3-month treatment period versus placebo. | Baseline - Month 3 | 
| Migraine Specific Quality of Life Questionnaire (MSQ) | Assess the change in MSQ Questionnaire scores from baseline to end of treatment period versus placebo. | Baseline - Month 3 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Migraine, Homeopathy, Individualized, Triple blind, Randomized, Clinical trial, headache