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

Cluster Headache Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04570475
• Other study ID #: HSC-MS-20-0945
• Status: Recruiting
• Phase: Phase 3
• Start date: September 15, 2021
• Est. completion date: June 22, 2026

Study information

• Verified date: November 2023
• Source: The University of Texas Health Science Center, Houston
• Contact: Mark J Burish, MD,PhD
• Phone: (713) 486-7771
• Email: nctt.wec[@]uth.tmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 220
• Est. completion date: June 22, 2026
• Est. primary completion date: November 22, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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:

1. 25-hydroxyvitamin D levels >75 nmol/L

2. Elevated calcium level

3. Elevated phosphate level

4. Abnormal parathyroid hormone levels

5. Elevated creatinine level

6. 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.

Related Conditions & MeSH terms

• Cluster Headache
• Headache

Intervention

Drug:
• Vitamin D
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.
• multivitamin
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.
• Placebo
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.

Locations

Country	Name	City	State
United States	The University of Texas Health Science Center at Houston	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
The University of Texas Health Science Center, Houston

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in average weekly frequency of cluster headache attacks	First primary outcome	(baseline, average of weeks 1-3)
Primary	Change in average weekly frequency of cluster headache attacks	Second primary outcome	(baseline, week 3)
Secondary	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)
Secondary	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
Secondary	Change in number of abortive medications or other treatments used per week		baseline, week 3
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in duration of cluster headache attacks, in minutes		baseline, week 3
Secondary	Change in level of 25-hydroxyvitamin D		baseline, week 3
Secondary	Change in average weekly frequency of cluster headache attacks		(baseline, week 6)
Secondary	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)
Secondary	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
Secondary	Change in number of abortive medications or other treatments used per week		baseline, week 6
Secondary	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
Secondary	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
Secondary	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
Secondary	Change in duration of cluster headache attacks, in minutes		baseline, week 6
Secondary	Change in level of 25-hydroxyvitamin D		baseline, week 6
Secondary	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
Secondary	Change in average weekly frequency of cluster headache attacks		(baseline, week 2)
Secondary	Change in average weekly frequency of cluster headache attacks		(baseline, week 1)
Secondary	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
Secondary	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
Secondary	Change in duration of cluster headache attacks, in minutes		baseline, week 2
Secondary	Change in duration of cluster headache attacks, in minutes		baseline, week 1
Secondary	Change in number of abortive medications or other treatments used per week		baseline, week 2
Secondary	Change in number of abortive medications or other treatments used per week		baseline, week 1
Secondary	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
Secondary	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
Secondary	Change in level of 25-hydroxyvitamin D		baseline, week 2
Secondary	Change in level of 25-hydroxyvitamin D		baseline, week 1
Secondary	Change in level of calcium		baseline, week 3
Secondary	Change in level of calcium		baseline, week 6
Secondary	Change in level of calcium		baseline, week 2
Secondary	Change in level of calcium		baseline, week 1
Secondary	Change in level of phosphate		baseline, week 3
Secondary	Change in level of phosphate		baseline, week 6
Secondary	Change in level of phosphate		baseline, week 1
Secondary	Change in level of phosphate		baseline, week 2
Secondary	Change in level of parathyroid hormone		baseline, week 3
Secondary	Change in level of parathyroid hormone		baseline, week 6
Secondary	Change in level of parathyroid hormone		baseline, week 1
Secondary	Change in level of parathyroid hormone		baseline, week 2
Secondary	Change in level of creatinine		baseline, week 3
Secondary	Change in level of creatinine		baseline, week 6
Secondary	Change in level of creatinine		baseline, week 1
Secondary	Change in level of creatinine		baseline, week 2
Secondary	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
Secondary	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