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

November 27, 2023 updated by: Mark J Burish, The University of Texas Health Science Center, Houston

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

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.

Study Overview

Status

Recruiting

Conditions

Study Type

Interventional

Enrollment (Estimated)

220

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • The University of Texas Health Science Center at Houston
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: vitamin D+multivitamin
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.
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.
Active Comparator: placebo+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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in average weekly frequency of cluster headache attacks
Time Frame: (baseline, average of weeks 1-3)
First primary outcome
(baseline, average of weeks 1-3)
Change in average weekly frequency of cluster headache attacks
Time Frame: (baseline, week 3)
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
Time Frame: (baseline, 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
Time Frame: baseline, week 3
baseline, week 3
Change in number of abortive medications or other treatments used per week
Time Frame: baseline, week 3
baseline, week 3
Change in intensity of cluster headache attacks as assessed by numerical rating scale
Time Frame: baseline, week 3
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
Time Frame: baseline, week 3
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
Time Frame: baseline, week 3
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
Time Frame: baseline, week 3
baseline, week 3
Change in level of 25-hydroxyvitamin D
Time Frame: baseline, week 3
baseline, week 3
Change in average weekly frequency of cluster headache attacks
Time Frame: (baseline, week 6)
(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
Time Frame: (baseline, 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
Time Frame: baseline, week 6
baseline, week 6
Change in number of abortive medications or other treatments used per week
Time Frame: baseline, week 6
baseline, week 6
Change in intensity of cluster headache attacks as assessed by numerical rating scale
Time Frame: baseline, week 6
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
Time Frame: baseline, week 6
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
Time Frame: baseline, week 6
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
Time Frame: baseline, week 6
baseline, week 6
Change in level of 25-hydroxyvitamin D
Time Frame: baseline, week 6
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)
Time Frame: upto 3 weeks from treatment
upto 3 weeks from treatment
Change in average weekly frequency of cluster headache attacks
Time Frame: (baseline, week 2)
(baseline, week 2)
Change in average weekly frequency of cluster headache attacks
Time Frame: (baseline, week 1)
(baseline, week 1)
Change in intensity of cluster headache attacks as assessed by numerical rating scale
Time Frame: baseline, week 2
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
Time Frame: baseline, week 1
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
Time Frame: baseline, week 2
baseline, week 2
Change in duration of cluster headache attacks, in minutes
Time Frame: baseline, week 1
baseline, week 1
Change in number of abortive medications or other treatments used per week
Time Frame: baseline, week 2
baseline, week 2
Change in number of abortive medications or other treatments used per week
Time Frame: baseline, week 1
baseline, week 1
Change in quality of life as measured by the Cluster Headache Quality of life questionnaire
Time Frame: baseline, week 2
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
Time Frame: baseline, week 1
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
Time Frame: baseline, week 2
baseline, week 2
Change in level of 25-hydroxyvitamin D
Time Frame: baseline, week 1
baseline, week 1
Change in level of calcium
Time Frame: baseline, week 3
baseline, week 3
Change in level of calcium
Time Frame: baseline, week 6
baseline, week 6
Change in level of calcium
Time Frame: baseline, week 2
baseline, week 2
Change in level of calcium
Time Frame: baseline, week 1
baseline, week 1
Change in level of phosphate
Time Frame: baseline, week 3
baseline, week 3
Change in level of phosphate
Time Frame: baseline, week 6
baseline, week 6
Change in level of phosphate
Time Frame: baseline, week 1
baseline, week 1
Change in level of phosphate
Time Frame: baseline, week 2
baseline, week 2
Change in level of parathyroid hormone
Time Frame: baseline, week 3
baseline, week 3
Change in level of parathyroid hormone
Time Frame: baseline, week 6
baseline, week 6
Change in level of parathyroid hormone
Time Frame: baseline, week 1
baseline, week 1
Change in level of parathyroid hormone
Time Frame: baseline, week 2
baseline, week 2
Change in level of creatinine
Time Frame: baseline, week 3
baseline, week 3
Change in level of creatinine
Time Frame: baseline, week 6
baseline, week 6
Change in level of creatinine
Time Frame: baseline, week 1
baseline, week 1
Change in level of creatinine
Time Frame: baseline, week 2
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
Time Frame: baseline, week 2
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
Time Frame: baseline, week 1
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Mark J Burish, MD,PhD, The University of Texas Health Science Center, Houston

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 15, 2021

Primary Completion (Estimated)

November 22, 2025

Study Completion (Estimated)

June 22, 2026

Study Registration Dates

First Submitted

September 25, 2020

First Submitted That Met QC Criteria

September 25, 2020

First Posted (Actual)

September 30, 2020

Study Record Updates

Last Update Posted (Actual)

November 28, 2023

Last Update Submitted That Met QC Criteria

November 27, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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