High Dose Vitamin D Plus Multivitamin in the Prevention of Cluster Headache

Study Overview
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Brief Summary
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This study intends to investigate the use of high-dose Vitamin D3 plus a multivitamin in the prevention of cluster headache attacks. Participants can be enrolled anywhere in the United States that has access to one of our participating labs (for blood work - anticipated to be available in most of the USA). The study may include: Screening: Participants may be interviewed, examined, fill out surveys, and get blood testing Week 1: baseline period (no added medications - to establish a baseline) Weeks 2-4: double-blinded experimental period - participants receive either 1) high-dose Vitamin D3 + multivitamin, or 2) placebo + multivitamin. Participants also fill out a survey and have blood testing. Weeks 5-7: open-label period - ALL participants receive high-dose Vitamin D3 + multivitamin. Participants also fill out a survey and may have blood testing. Specifically, our primary outcome is the change from baseline to experimental weeks 1-3 in the frequency of cluster headache attacks between placebo and high-dose vitamin D. Specific primary and secondary outcomes are listed below.

Official Title
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High Dose Vitamin D Plus Multivitamin in the Prevention of Cluster Headache: a Randomized, Double-blind, Placebo Controlled Trial.

Conditions
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Cluster Headache

Intervention / Treatment
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* Drug: Vitamin D
* Drug: multivitamin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A diagnosis of episodic cluster headache according to the International Classification of Headache Disorders 3rd edition as well as cluster periods that are predictable and have a duration of 6 weeks or greater and approximately one attack daily minimum OR A diagnosis of chronic cluster headache according to the International Classification of Headache Disorders 3rd edition as well as approximately one attack daily Participants who are unlikely to need to change their preventive cluster headache treatment regimen in the next 6 weeks. Exclusion Criteria: Co-existing disease or other characteristic that precludes appropriate diagnosis of cluster headache. Active drug or alcohol use or dependence that, in the opinion of the site investigator,would interfere with adherence to study requirements. Inability or unwillingness of subject to give informed consent. Known allergy to study drug, multivitamin, or placebo components Pregnancy or lactation (breastfeeding) Usage of greater than 4,000 International Units of Vitamin D3 daily within 60 days of the beginning of the study. Concurrent use of Vitamin D and/or multivitamin along with the inability to stop them before the study begins. Liver failure or known coagulation disorder (as this study includes vitamin K) such as haemophilia, von Willebrand disease, Factor V Leiden, Antithrombin III deficiency, Protein C or S deficiency, or anti-phospholipid antibody syndrome. A personal medical history of more than 1 deep venous thrombosis and/or pulmonary embolism (as this study includes vitamin K). Current use of anticoagulants (as this study includes vitamin K). Anticoagulants include: apixaban (Eliquis), betrixaban (Bevyxxa), dabigatran (Pradaxa), dalteparin (Fragmin), edoxaban (Savaysa), enoxaparin (Lovenox), fondaparinux (Arixtra), heparin, rivaroxiban (Xarelto), and warfarin (Coumadin). Current use of medications that alter vitamin D metabolism, including steroids,interferon, phenytoin, phenobarbital, digitalis/digoxin, and thiazide diuretics (such as hydrochlorothiazide or chlorthalidone) Participants who are aware that their most recent labwork in the last 2 years showed any of the following: 25-hydroxyvitamin D levels >75 nmol/L Elevated calcium level Elevated phosphate level Abnormal parathyroid hormone levels Elevated creatinine level Of note if any values are outside the acceptable range for the study, candidates may still participate in the study if the most recent lab testing is inside the acceptable range for the study. For example, if a candididate were taking a vitamin or medication that may have caused these elevated levels, but no longer take the vitamin or medication, they may be enrolled if retesting is normal.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vitamin D+multivitamin<br> | Drug: Vitamin D<br>* Participants will receive vitamin D+multivitamin for 3 weeks. At the end of 3 weeks they will complete an online or paper questionnaire and blood work will be done.<br>Drug: multivitamin<br>* Participants will receive placebo+multivitamin or vitamin D+multivitamin for 3 weeks. At the end of 3 weeks they will complete an online or paper questionnaire and blood work will be done.<br>|
| Active Comparator: placebo+multivitamin<br> | Drug: multivitamin<br>* Participants will receive placebo+multivitamin or vitamin D+multivitamin for 3 weeks. At the end of 3 weeks they will complete an online or paper questionnaire and blood work will be done.<br>Drug: Placebo<br>* Participants will receive placebo+multivitamin for 3 weeks. At the end of 3 weeks they will complete an online or paper questionnaire and blood work will be done.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in average weekly frequency of cluster headache attacks | First primary outcome | (baseline, average of weeks 1-3) | 
| Change in average weekly frequency of cluster headache attacks | Second primary outcome | (baseline, week 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who had a reduction of at least 50% in the weekly frequency of cluster headache attacks between baseline and week 3 |  | (baseline, week 3) | 
| Number of participants who had a reduction of at least 30% in the weekly frequency of cluster headache attacks between baseline and week 3 |  | baseline, week 3 | 
| Change in number of abortive medications or other treatments used per week |  | baseline, week 3 | 
| Change in intensity of cluster headache attacks as assessed by numerical rating scale | Total score ranges from 0-10, and a higher score indicates a greater intensity of attacks | baseline, week 3 | 
| Change in number of participants whose disease is 'much better' or 'very much better' as assessed by the Patient Global Impression of Improvement Scale | With the Patient Global Impression of Improvement Scale, a patient is asked to rate their disease as Very much better, Much better, A little better, No change, A little worse, Much worse, or Very much worse compared to a reference point in the past | baseline, week 3 | 
| Change in quality of life as measured by the Cluster Headache Quality of life questionnaire | Total score ranges from 0-100, and a higher score indicates a better quality of life | baseline, week 3 | 
| Change in duration of cluster headache attacks, in minutes |  | baseline, week 3 | 
| Change in level of 25-hydroxyvitamin D |  | baseline, week 3 | 
| Change in average weekly frequency of cluster headache attacks |  | (baseline, week 6) | 
| Number of participants who had a reduction of at least 50% in the weekly frequency of cluster headache attacks between baseline and week 6 |  | (baseline, week 6) | 
| Number of participants who had a reduction of at least 30% in the weekly frequency of cluster headache attacks between baseline and week 6 |  | baseline, week 6 | 
| Change in number of abortive medications or other treatments used per week |  | baseline, week 6 | 
| Change in intensity of cluster headache attacks as assessed by numerical rating scale | Total score ranges from 0-10, and a higher score indicates a greater intensity of attacks | baseline, week 6 | 
| Change in number of participants whose disease is 'much better' or 'very much better' as assessed by the Patient Global Impression of Improvement Scale | With the Patient Global Impression of Improvement Scale, a patient is asked to rate their disease as Very much better, Much better, A little better, No change, A little worse, Much worse, or Very much worse compared to a reference point in the past | baseline, week 6 | 
| Change in quality of life as measured by the Cluster Headache Quality of life questionnaire | Total score ranges from 0-100, and a higher score indicates a better quality of life | baseline, week 6 | 
| Change in duration of cluster headache attacks, in minutes |  | baseline, week 6 | 
| Change in level of 25-hydroxyvitamin D |  | baseline, week 6 | 
| Number of days until end of the cluster period after the start of treatment (i.e., the time to the end of an episodic cluster cycle) |  | upto 3 weeks from treatment | 
| Change in average weekly frequency of cluster headache attacks |  | (baseline, week 2) | 
| Change in average weekly frequency of cluster headache attacks |  | (baseline, week 1) | 
| Change in intensity of cluster headache attacks as assessed by numerical rating scale | Total score ranges from 0-10, and a higher score indicates a greater intensity of attacks | baseline, week 2 | 
| Change in intensity of cluster headache attacks as assessed by numerical rating scale | Total score ranges from 0-10, and a higher score indicates a greater intensity of attacks | baseline, week 1 | 
| Change in duration of cluster headache attacks, in minutes |  | baseline, week 2 | 
| Change in duration of cluster headache attacks, in minutes |  | baseline, week 1 | 
| Change in number of abortive medications or other treatments used per week |  | baseline, week 2 | 
| Change in number of abortive medications or other treatments used per week |  | baseline, week 1 | 
| Change in quality of life as measured by the Cluster Headache Quality of life questionnaire | Total score ranges from 0-100, and a higher score indicates a better quality of life | baseline, week 2 | 
| Change in quality of life as measured by the Cluster Headache Quality of life questionnaire | Total score ranges from 0-100, and a higher score indicates a better quality of life | baseline, week 1 | 
| Change in level of 25-hydroxyvitamin D |  | baseline, week 2 | 
| Change in level of 25-hydroxyvitamin D |  | baseline, week 1 | 
| Change in level of calcium |  | baseline, week 3 | 
| Change in level of calcium |  | baseline, week 6 | 
| Change in level of calcium |  | baseline, week 2 | 
| Change in level of calcium |  | baseline, week 1 | 
| Change in level of phosphate |  | baseline, week 3 | 
| Change in level of phosphate |  | baseline, week 6 | 
| Change in level of phosphate |  | baseline, week 1 | 
| Change in level of phosphate |  | baseline, week 2 | 
| Change in level of parathyroid hormone |  | baseline, week 3 | 
| Change in level of parathyroid hormone |  | baseline, week 6 | 
| Change in level of parathyroid hormone |  | baseline, week 1 | 
| Change in level of parathyroid hormone |  | baseline, week 2 | 
| Change in level of creatinine |  | baseline, week 3 | 
| Change in level of creatinine |  | baseline, week 6 | 
| Change in level of creatinine |  | baseline, week 1 | 
| Change in level of creatinine |  | baseline, week 2 | 
| Change in number of participants whose disease is 'much better' or 'very much better' as assessed by the Patient Global Impression of Improvement Scale | With the Patient Global Impression of Improvement Scale, a patient is asked to rate their disease as Very much better, Much better, A little better, No change, A little worse, Much worse, or Very much worse compared to a reference point in the past | baseline, week 2 | 
| Change in number of participants whose disease is 'much better' or 'very much better' as assessed by the Patient Global Impression of Improvement Scale | With the Patient Global Impression of Improvement Scale, a patient is asked to rate their disease as Very much better, Much better, A little better, No change, A little worse, Much worse, or Very much worse compared to a reference point in the past | baseline, week 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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headache, trigeminal autonomic cephalalgia, chronic cluster headache, episodic cluster headache