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

• ClinicalTrials.gov Identifier: NCT04570475
• Recruitment Status: Recruiting
• First Posted: September 30, 2020
• Last Update Posted: November 28, 2023
• Sponsor: The University of Texas Health Science Center, Houston
• Information provided by (Responsible Party): Mark J Burish, The University of Texas Health Science Center, Houston

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Cluster Headache	Drug: Vitamin D; Drug: multivitamin; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 220 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: High Dose Vitamin D Plus Multivitamin in the Prevention of Cluster Headache: a Randomized, Double-blind, Placebo Controlled Trial.
• Actual Study Start Date: September 15, 2021
• Estimated Primary Completion Date: November 22, 2025
• Estimated Study Completion Date: June 22, 2026

Arms and Interventions

Arm	Intervention/treatment
Experimental: vitamin D+multivitamin	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.; Drug: 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.
Active Comparator: placebo+multivitamin	Drug: 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.; Drug: 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.

Outcome Measures

Primary Outcome Measures :

1. Change in average weekly frequency of cluster headache attacks [ Time Frame: (baseline, average of weeks 1-3) ]
   First primary outcome
2. Change in average weekly frequency of cluster headache attacks [ Time Frame: (baseline, week 3) ]
   Second primary outcome

Secondary Outcome Measures :

1. 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) ]
2. 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 ]
3. Change in number of abortive medications or other treatments used per week [ Time Frame: baseline, week 3 ]
4. 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
5. 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
6. 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
7. Change in duration of cluster headache attacks, in minutes [ Time Frame: baseline, week 3 ]
8. Change in level of 25-hydroxyvitamin D [ Time Frame: baseline, week 3 ]
9. Change in average weekly frequency of cluster headache attacks [ Time Frame: (baseline, week 6) ]
10. 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) ]
11. 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 ]
12. Change in number of abortive medications or other treatments used per week [ Time Frame: baseline, week 6 ]
13. 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
14. 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
15. 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
16. Change in duration of cluster headache attacks, in minutes [ Time Frame: baseline, week 6 ]
17. Change in level of 25-hydroxyvitamin D [ Time Frame: baseline, week 6 ]
18. 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 ]
19. Change in average weekly frequency of cluster headache attacks [ Time Frame: (baseline, week 2) ]
20. Change in average weekly frequency of cluster headache attacks [ Time Frame: (baseline, week 1) ]
21. 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
22. 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
23. Change in duration of cluster headache attacks, in minutes [ Time Frame: baseline, week 2 ]
24. Change in duration of cluster headache attacks, in minutes [ Time Frame: baseline, week 1 ]
25. Change in number of abortive medications or other treatments used per week [ Time Frame: baseline, week 2 ]
26. Change in number of abortive medications or other treatments used per week [ Time Frame: baseline, week 1 ]
27. 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
28. 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
29. Change in level of 25-hydroxyvitamin D [ Time Frame: baseline, week 2 ]
30. Change in level of 25-hydroxyvitamin D [ Time Frame: baseline, week 1 ]
31. Change in level of calcium [ Time Frame: baseline, week 3 ]
32. Change in level of calcium [ Time Frame: baseline, week 6 ]
33. Change in level of calcium [ Time Frame: baseline, week 2 ]
34. Change in level of calcium [ Time Frame: baseline, week 1 ]
35. Change in level of phosphate [ Time Frame: baseline, week 3 ]
36. Change in level of phosphate [ Time Frame: baseline, week 6 ]
37. Change in level of phosphate [ Time Frame: baseline, week 1 ]
38. Change in level of phosphate [ Time Frame: baseline, week 2 ]
39. Change in level of parathyroid hormone [ Time Frame: baseline, week 3 ]
40. Change in level of parathyroid hormone [ Time Frame: baseline, week 6 ]
41. Change in level of parathyroid hormone [ Time Frame: baseline, week 1 ]
42. Change in level of parathyroid hormone [ Time Frame: baseline, week 2 ]
43. Change in level of creatinine [ Time Frame: baseline, week 3 ]
44. Change in level of creatinine [ Time Frame: baseline, week 6 ]
45. Change in level of creatinine [ Time Frame: baseline, week 1 ]
46. Change in level of creatinine [ Time Frame: baseline, week 2 ]
47. 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
48. 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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Mark J Burish, MD,PhD; (713) 486-7771; nctt.wec@uth.tmc.edu

Contact: Celia Tran, BS; (713) 486-7771; nctt.wec@uth.tmc.edu

Locations

United States, Texas

The University of Texas Health Science Center at Houston; Recruiting

Houston, Texas, United States, 77030

Contact: Mark J Burish, MD,PhD 713-486-7771 nctt.wec@uth.tmc.edu

Contact: Celia Tran, BS (713) 486-7771 nctt.wec@uth.tmc.edu

Sponsors and Collaborators

The University of Texas Health Science Center, Houston

Investigators

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

More Information

• Responsible Party: Mark J Burish, Assistant Professor, The University of Texas Health Science Center, Houston
• ClinicalTrials.gov Identifier: NCT04570475
• Other Study ID Numbers: HSC-MS-20-0945
• First Posted: September 30, 2020
• Last Update Posted: November 28, 2023
• Last Verified: November 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Mark J Burish, The University of Texas Health Science Center, Houston:

headache; trigeminal autonomic cephalalgia; chronic cluster headache; episodic cluster headache

Additional relevant MeSH terms:

Cluster Headache; Headache; Pain; Neurologic Manifestations; Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vitamin D; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents