Idebenone for the Preventive Treatment of Migraine

November 28, 2023 updated by: Kaiming Liu, Second Affiliated Hospital, School of Medicine, Zhejiang University

A Randomized, Double-blinded, Placebo-controlled Trial of Idebenone in the Prevention of Episodic Migraine

Idebenone improves energy metabolism similarly to Coenzyme Q10, which is effective in migraine prophylaxis. The investigators compare idebenone (90 mg/day, 270 mg/day) and placebo in 180 migraine patients in a double-blind, randomized, placebo-controlled, multicenter trial to study whether Idebenone is superior to placebo in the prevention of episodic migraine with or without aura.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

One-hundred-and-eighty subjects will be recruited for a placebo-controlled, double-blinded study of idebenone (90 mg/day, 270 mg/day) versus placebo. One-hundred-and-eighty subjects will be recruited based on past research and an expected 20% dropout rate. A dose of 90mg or 270 mg is based on large number of reports at study initiation in Leber's hereditary optic neuropathy that demonstrated the safety of 900mg/day. Subjects are 18 to 65 years old, inclusive, who meet the International Classification of Headache Disorder- III (ICHD-III) for episodic migraine with or without aura, no over consumption of acute anti-migraine medication, no other prophylactic medication (washout 3 months), no serious organic or psychiatric disease, who are recommended to start prophylactic therapy (two to eight attacks per month). Written informed consent is obtained. The process of patients through the trial phases follows the CONSORT flow chart.

Idebenone and placebo were provided by Qilu Pharmaceutical Company Limited, China. Placebo consisted of the same ingredients as verum-instead idebenone, they classify as fit for human consumption in the China and without any known effect on migraine.

The design of this double-blind, randomized, placebo-controlled trial followed the IHS Committee on Clinical Trials in Migraine guidelines, 8 current EU guidelines on Good Clinical Practice, and the Declaration of Helsinki. It was approved by Neurology Department, the Second Affiliated Hospital, School of Medicine, Zhejiang University. This study is supported by the following funding sources: the Zhejiang Provincial Natural Science Foundation of China (Grant No. LY19H090025, Grant No. LQ15H090003), the National Natural Science Foundation of China (Grant No. 81101157). The study is also supported by Qilu Pharmaceutical Company Limited, China (http://www.qilu-pharma.com); the use of idebenone in migraine, is patent pending in the China. Dr. Kaiming Liu do not receive honoraria from the sponsor of the study.

Exclusion criteria includes subjects who previously failed idebenone therapy for migraine prophylaxis, those who previously discontinued idebenone due to adverse events, those who are taking idebenone or had taken idebenone within 14 days prior to enrollment, and subjects with continuous headaches. Subjects will be equally randomized to be treated with 90 mg/day idebenone, 270 mg/day idebenone, or placebo for 3 months.

At the first visit, patients will receive placebo for a 1-month base-line. At the second visit, they will be randomized to be treated with 90 mg/day idebenone, 270 mg/day idebenone, or placebo for next 3 months if they have presented at least one migraine attack.

The primary objective is to assess whether at least 1 dose of Idebenone is superior to placebo in overall mean change from baseline of 4-week migraine headache days (MHD) during double-blind treatment. Key secondary outcome variables will be change of migraine attack frequency, migraine moderate/severe headache days, the proportion of subjects with at least 50%, at least 75%, and 100% reduction in migraine days, mean severity of migraine, acute treatment utilization, quality of life related to episodic migraine as measured by the The Role Function Physical subscale in The Migraine-Specific Quality of Life questionnaire (MSQ v2.1), migraine-related disability as measured by The Headache Impact Test (HIT-6), Patient Global Impression of Severity (PGI-S) scores, and Migraine Disability Assessment (MIDAS) scores from baseline of 4-week to the entire double-blind treatment phase.

Responders for attack frequency (50% reduction) will be calculated and the number-needed-to-treat (NNT) determined. Patients will be interviewed about adverse events at each visit. Statistical analysis will be done on an intention-to-treat population applying the last visit carried forward method. Mann-Whitney U test will be used for differences between groups, 2 test for 22 contingency tables of responder rate, general linear mixed model for evolution over time. Significance level is p<0.05, after accounting for multiple comparisons. SPSS will be used.

Study Type

Interventional

Enrollment (Estimated)

180

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 Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China, 370001
        • Recruiting
        • Kaiming Liu
        • Contact:
          • Kaiming Liu

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

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Clinical diagnosis of episodic migraine.
  2. Patients (18-65 years) were eligible if they met International Headache Society (IHS) criteria for episodic migraine with/ without aura with a migraine history 1 year
  3. Two to eight attacks per month, 5 days/month of interval headaches.
  4. No over consumption of acute anti-migraine medication.
  5. No other prophylactic medication (washout 3 months).
  6. No serious organic or psychiatric disease.
  7. Only women with contraceptive protection.

Exclusion Criteria:

  1. Clinical diagnosis of chronic migraine.
  2. Subjects previously discontinued idebenone due to adverse events.
  3. Subjects are taking idebenone or had taken idebenone within 14 days prior to enrollment.
  4. Subjects with continuous headaches.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 90mg Idebenone
Placebo by mouth, three times a day for 1 months； Idebenone 30mg table by mouth, three times a day for next 3 months
Drug: Placebo
Placebo oral tablet, three times a day
Drug: 90mg Idebenone
Idebenone 30 MG Oral Tablet, three times a day
Other Names:
  • Shenwei
Experimental: 270mg Idebenone
Placebo by mouth, three times a day for 1 months； Idebenone 90mg table by mouth, three times a day for next 3 months
Drug: Placebo
Placebo oral tablet, three times a day
Drug: 270mg Idebenone
Idebenone 90 MG Oral Tablet, three times a day
Other Names:
  • Shenwei
Placebo Comparator: Placebo
Placebo by mouth, three times a day for 4 months
Drug: Placebo
Placebo oral tablet, three times a day

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change of migraine attack frequency
Time Frame: month 0, month 1, month 2, month 3, month 4
The change of migraine attack frequency in month 4 compared with baseline. Headache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary. Degree of pain and results of treatment are scored by visual analogue scale(VAS).
month 0, month 1, month 2, month 3, month 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The change of days with headache
Time Frame: month 0, month 1, month 2, month 3, month 4
The change of days with headache per month compared with baseline. Headache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary.
month 0, month 1, month 2, month 3, month 4
Mean severity of migraine
Time Frame: month 0, month 1, month 2, month 3, month 4
Mean severity of migraine per month compared with baselineHeadache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary. Degree of pain is scored by VAS.
month 0, month 1, month 2, month 3, month 4
The change of days with nausea/vomiting
Time Frame: month 0, month 1, month 2, month 3, month 4
The change of days with nausea/vomiting per month compared with baselineHeadache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary.
month 0, month 1, month 2, month 3, month 4
Mean duration of migraine
Time Frame: month 0, month 1, month 2, month 3, month 4
Mean duration of migraine per month compared with baselineHeadache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary.
month 0, month 1, month 2, month 3, month 4
50% Responder rate for attack frequency
Time Frame: month 0, month 1, month 2, month 3, month 4
50% Responder rate for attack frequency compared with baselineHeadache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary.
month 0, month 1, month 2, month 3, month 4
Mean no. tablets per day
Time Frame: month 0, month 1, month 2, month 3, month 4
Mean no. tablets per day compared with baselineHeadache data (e.g., occurrence, duration, and pain severity; occurrence of photophobia, phonophobia, nausea, or vomiting; and any use of migraine medication) were captured daily through a daily headache-diary.
month 0, month 1, month 2, month 3, month 4

Collaborators and Investigators

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

Sponsor

Second Affiliated Hospital, School of Medicine, Zhejiang University

Investigators

  • Study Chair: Kaiming Liu, MD & PHD, Second Affiliated Hospital, School of Medicine, Zhejiang University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

December 8, 2021

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2025

Study Registration Dates

First Submitted

October 29, 2019

First Submitted That Met QC Criteria

November 2, 2019

First Posted (Actual)

November 5, 2019

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019-675

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Some subjects do not hope that their IPD are used by other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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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