Idebenone for the Preventive Treatment of Migraine

Migraine Disorders Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04151472
• Other study ID #: 2019-675
• Status: Recruiting
• Phase: Phase 3
• Start date: December 8, 2021
• Est. completion date: December 31, 2025

Study information

• Verified date: November 2023
• Source: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Contact: Kaiming Liu, MD & PHD
• Phone: +8615068862055
• Email: 2314411[@]zju.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Headache
• Headache Disorders
• Migraine Disorders

Intervention

Drug:
• Placebo
Placebo oral tablet, three times a day
• 90mg Idebenone
Idebenone 30 MG Oral Tablet, three times a day
• 270mg Idebenone
Idebenone 90 MG Oral Tablet, three times a day

Locations

Country	Name	City	State
China	Kaiming Liu	Hangzhou	Zhejiang

Sponsors (1)

Lead Sponsor	Collaborator
Second Affiliated Hospital, School of Medicine, Zhejiang University

Country where clinical trial is conducted

China, 

References & Publications (11)

Borkum JM. Migraine Triggers and Oxidative Stress: A Narrative Review and Synthesis. Headache. 2016 Jan;56(1):12-35. doi: 10.1111/head.12725. Epub 2015 Dec 7. — View Citation

Brenner SR. Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology. 2010 Jan 12;74(2):182-3; author reply 183. doi: 10.1212/WNL.0b013e3181c77678. No abstract available. — View Citation

Dahri M, Tarighat-Esfanjani A, Asghari-Jafarabadi M, Hashemilar M. Oral coenzyme Q10 supplementation in patients with migraine: Effects on clinical features and inflammatory markers. Nutr Neurosci. 2019 Sep;22(9):607-615. doi: 10.1080/1028415X.2017.142103 — View Citation

Dalla Volta G, Carli D, Zavarise P, Ngonga G, Vollaro S. P026. Pilot study on the use of coenzyme Q10 in a group of patients with episodic migraine without aura. J Headache Pain. 2015 Dec;16(Suppl 1):A186. doi: 10.1186/1129-2377-16-S1-A186. No abstract av — View Citation

Gaul C, Diener HC, Danesch U; Migravent(R) Study Group. Improvement of migraine symptoms with a proprietary supplement containing riboflavin, magnesium and Q10: a randomized, placebo-controlled, double-blind, multicenter trial. J Headache Pain. 2015;16:51 — View Citation

Klopstock T, Yu-Wai-Man P, Dimitriadis K, Rouleau J, Heck S, Bailie M, Atawan A, Chattopadhyay S, Schubert M, Garip A, Kernt M, Petraki D, Rummey C, Leinonen M, Metz G, Griffiths PG, Meier T, Chinnery PF. A randomized placebo-controlled trial of idebenone — View Citation

Koreshkina MI. [The use of noben (idebenone) in the complex treatment of episodic and chronic migraine]. Zh Nevrol Psikhiatr Im S S Korsakova. 2010;110(6):98-101. No abstract available. Russian. — View Citation

Markley HG. CoEnzyme Q10 and riboflavin: the mitochondrial connection. Headache. 2012 Oct;52 Suppl 2:81-7. doi: 10.1111/j.1526-4610.2012.02233.x. — View Citation

Rozen TD, Oshinsky ML, Gebeline CA, Bradley KC, Young WB, Shechter AL, Silberstein SD. Open label trial of coenzyme Q10 as a migraine preventive. Cephalalgia. 2002 Mar;22(2):137-41. doi: 10.1046/j.1468-2982.2002.00335.x. — View Citation

Slater SK, Nelson TD, Kabbouche MA, LeCates SL, Horn P, Segers A, Manning P, Powers SW, Hershey AD. A randomized, double-blinded, placebo-controlled, crossover, add-on study of CoEnzyme Q10 in the prevention of pediatric and adolescent migraine. Cephalalg — View Citation

Yorns WR Jr, Hardison HH. Mitochondrial dysfunction in migraine. Semin Pediatr Neurol. 2013 Sep;20(3):188-93. doi: 10.1016/j.spen.2013.09.002. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The change of migraine attack frequency	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	The change of days with headache	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
Secondary	Mean severity of migraine	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
Secondary	The change of days with nausea/vomiting	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
Secondary	Mean duration of migraine	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
Secondary	50% Responder rate for attack frequency	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
Secondary	Mean no. tablets per day	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