TIzanidine for the Preventive Treatment of Episodic MigrainE （TIME）

NCT05484349 | Recruiting Phase 3 DMC

• 1 other identifier: 2022-0622
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 6

Brief Summary

In this study,189 adult migraine patients aged 18-65 years (diagnosed with migraine without aura and/or migraine with aura, with at least a 1-year history)will be collected to evaluate the efficacy, safety and tolerability of Tizanidine Hydrochloride in preventing migraine attacks in episodic migraine in adults.

Conditions

Migraine Without Aura; Migraine With Aura

Keywords

Migraine; Migraine Without Aura; Migraine With Aura

Outcome Measures

Primary Outcomes (1)

• The Change of Migraine Days.

  The change of migraine days per 4 weeks during the 12-week treatment period mpared with baseline.Baseline refers to the frequency of migraine attacks within the 28 days prior to randomization (baseline period, i.e., D-28 to D-1). Headache data were captured through an electronic diary.

  12-week treatment period（Day 1-Day 84）

Secondary Outcomes (19)

• The Change of Headache Attack Frequency

  12-week treatment period（Day 1-Day 84）

• The Change of Moderate / Severe Headache Days

  12-week treatment period（Day 1-Day 84）

• The Responder Rate of at Least 50%, 75% and 100% Reduction of Migraine Days.

  12-week treatment period（Day 1-Day 84）

• The Change of Frequency of Medications Use

  12-week treatment period（Day 1-Day 84）

• The Change of Peak Headache Pain Intensity

  12-week treatment period（Day 1-Day 84）

Study Arms (3)

group A

EXPERIMENTAL

Tizanidine Hydrochloride 1 mg Tid

Drug: Tizanidine Hydrochloride

group B

EXPERIMENTAL

Tizanidine Hydrochloride 2 mg Tid

Drug: Tizanidine Hydrochloride

group C

PLACEBO COMPARATOR

placebo 1 tablet Tid

Drug: Tizanidine Hydrochloride Placebo

Interventions

Tizanidine Hydrochloride DRUG

Tizanidine Hydrochloride 1 mg Tid for 12 consecutive weeks and were followed up for 12 weeks

group A

Tizanidine Hydrochloride Placebo DRUG

Tizanidine Hydrochloride Placebo Comparator 1 tablet Tid for 12 consecutive weeks and were followed up for 12 weeks

group C

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The age at entry for trails involving adult subjects is 18-65 years (including both ends)；
• According to ICHD-3(Headache Classification Committee of the International Headache Society,2018), individuals should be diagnosed with migraine without aura and/or migraine with aura, and should have a history of at least 1 year;
• The age at first migraine onset should be \<50 years;
• Migraine attacks ≥ 4 days/month and \< 15 days/month within 3 months prior to screening period (Refer to the definition of migraine days);
• Within 3 months before entering the screening period, the number of headache (including migraine and other types of headache) attack days per month is less than 15 days/month (Refer to the definition of headache days);
• Be willing to take effective contraceptive measures during the period of participating in this experiment and within 28 days after the last time taking investigational product;
• Understand and abide by the research procedures and methods, voluntarily participate in this experiment, and sign the informed consent in writing, agreeing to enter the baseline period.
• The following criteria must be met during the baseline period to be eligible for entering the randomized, double-blind, placebo-controlled trial of the drug:
• Migraine days ≥4 and \<14 days within 4 weeks of baseline period(Evaluation based on the Annex 14.-Electronic Headache Diary);
• Headache days \< 14 days within 4 weeks of baseline period;
• Completion of at least 80% of the electronic diary within 4 weeks of the baseline period(Within 28 days of the baseline period, the electronic diary has been completed for at least 23 days), and the investigator believes that the subject is able to read, understand, and complete the study questionnaire and headache diary;
• Understand and abide by the research procedures and methods, voluntarily participate in this experiment, and sign the informed consent in writing, agreeing to enter the randomized, double-blind, placebo-controlled trials of the drug.

You may not qualify if:

• Subjects with any of the following cannot participate in this study:
• Subject diagnosed with possible migraine according to ICHD-3(2018);
• Current and previous diagnosis of primary headache, secondary headache, or painful cranial neuropathy other than migraine(diagnostic criteria are defined according to ICHD-3,2018);
• Previous use of more than two of the following 7 drugs is ineffective after adequate use, the types of these drugs are as follows:
• Type 1: Divalproex, Sodium Valproate
• Type 2: Topiramate
• Type 3: Beta blockers(such as: Atenolol, Bisoprolol, Metoprolol, Nadolol, Nebivolol, Pindolol, Propranolol, Timolol)
• Type 4: Tricyclic antidepressants(TCA) (such as: Amitriptyline, Nortriptyline, Protriptyline)
• Type 5: Serotonin-norepinephrine reuptake inhibitors (SNRIs) (such as: Venlafaxine, Desvenlafaxine, Duloxetine, Milnacipran)
• Type 6: Flunarizine, Verapamil
• Type 7: lisinopril, Candesartan
• Type 8: Drugs acting on the CGRP pathway（Monoclonal antibodies and Gepants）
• Definition of treatment failure: No reduction in headache frequency, duration, or severity after 6 weeks of administration of the above drugs.
• The following conditions are not defined as treatment failure:
• Lack of sustained response to medication;

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Sichuan Credit Pharmaceutical Co., Ltd.: collaborator

Study Sites (6)

The Affiliated Hospital of Southwest Medical University

Luzhou, Sichuan, China

NOT YET RECRUITING

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China

RECRUITING

Zhejiang Provincial People's Hospital

Hangzhou, Zhejiang, China

NOT YET RECRUITING

The First Hospital of Jiaxing

Jiaxing, Zhejiang, China

RECRUITING

Affiliated Hospital of Shaoxing University

Shaoxing, Zhejiang, China

ACTIVE NOT RECRUITING

Related Publications (8)

• Lai J, Dilli E. Migraine Aura: Updates in Pathophysiology and Management. Curr Neurol Neurosci Rep. 2020 May 19;20(6):17. doi: 10.1007/s11910-020-01037-3.

  PMID: 32430657 RESULT

• GBD 2017 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018 Nov 10;392(10159):1789-1858. doi: 10.1016/S0140-6736(18)32279-7. Epub 2018 Nov 8.

  PMID: 30496104 RESULT

• GBD 2016 Headache Collaborators. Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2018 Nov;17(11):954-976. doi: 10.1016/S1474-4422(18)30322-3.

  PMID: 30353868 RESULT

• GBD 2016 Neurology Collaborators. Global, regional, and national burden of neurological disorders, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 May;18(5):459-480. doi: 10.1016/S1474-4422(18)30499-X. Epub 2019 Mar 14.

  PMID: 30879893 RESULT

• Yu S, Liu R, Zhao G, Yang X, Qiao X, Feng J, Fang Y, Cao X, He M, Steiner T. The prevalence and burden of primary headaches in China: a population-based door-to-door survey. Headache. 2012 Apr;52(4):582-91. doi: 10.1111/j.1526-4610.2011.02061.x.

  PMID: 22590713 RESULT

• Liu R, Yu S, He M, Zhao G, Yang X, Qiao X, Feng J, Fang Y, Cao X, Steiner TJ. Health-care utilization for primary headache disorders in China: a population-based door-to-door survey. J Headache Pain. 2013 Jun 3;14(1):47. doi: 10.1186/1129-2377-14-47.

  PMID: 23731663 RESULT

• International Headache Congress (IHC), Dublin, Ireland; September 5th-8th, 2019.

  RESULT

• Luo N, Qi W, Zhuang C, Di W, Lu Y, Huang Z, Sun Y, Zhang A, Huang X, Tao Y, Zhu Y, Li A, Jiang Z, Massing MW, Fang Y. A satisfaction survey of current medicines used for migraine therapy in China: is Chinese patent medicine effective compared with Western medicine for the acute treatment of migraine? Pain Med. 2014 Feb;15(2):320-8. doi: 10.1111/pme.12277. Epub 2013 Nov 8.

  PMID: 24524844 RESULT

MeSH Terms

Conditions

Migraine without Aura; Migraine with Aura; Migraine Disorders

Interventions

tizanidine

Condition Hierarchy (Ancestors)

Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Kaiming Liu, MD & PHD

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  STUDY CHAIR

Central Study Contacts

Kaiming Liu, MD & PHD

CONTACT

+8615068862055; 2314411@zju.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: In this double blind clinical trial, Tizanidine Hydrochloride was identical in appearance to the Tizanidine Hydrochloride placebo. Patients, investigators (persons who screen patients, assess endpoints, and assess protocol compliance), and sponsor personnel associated with clinical research should be blinded.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: A total of 189 patients were planned to be enrolled, and all subjects were randomly assigned to group A (Tizanidine Hydrochloride 1 mg Tid) , group B (Tizanidine Hydrochloride 2 mg Tid) and group C (placebo 1 tablet Tid) according to a 1:1 :1ratio, with 63 subjects in each group.

Study Record Dates

• First Submitted: July 11, 2022
• First Posted: August 2, 2022
• Study Start: June 1, 2023
• Primary Completion: December 25, 2025
• Study Completion: December 25, 2025
• Last Updated: August 1, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (6)