Effectiveness and Neural Mechanism of Naoan Dripping Pills for Migraine (ENMNM)

Effectiveness and Neural Mechanism of Naoan Dripping Pills for Migraine: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

This is a randomized, double-blind, placebo-controlled clinical trial. Its main purpose is to investigate the effects and neural mechanism of Naoan dripping pills on migraine patients by utilizing fMRI and DTI method, as well as headache evaluation measures such as responder rate, headache duration, PRO scale, etc.

Study Overview

• Status: Completed
• Conditions: Migraine
• Intervention / Treatment: Drug: Naoan dripping pills; Drug: Placebo

Detailed Description

Naoan dripping pills, which is a Chinese patent medicine proved effectively in treating migraine on clinic, but its neural mechanism remains unknown. This study is expected to validate the effectiveness and explore its neural mechanism by fMRI and DTI so as to provide evidence for physicians to promote the appropriate use of Naoan dripping pills treatment for migraine patients. Patients will be randomly assigned to either Naoan dripping pills group or placebo group, they will receive Naoan dripping pills/Placebo treatment for 12 weeks. Clinical evaluation will be performed at baseline, every 4 weeks during treatment and the follow-up week(16 weeks) . MRI scans are performed at baseline, and 12 weeks later. Responder rate (defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period) and fMRI and DTI imaging changes after treatment are defined as primary outcome. In addition, 10 healthy controls will also undergo MRI scanning at baseline to determine abnormal brain activity and structure in migraine patients.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100700
      • Dongzhimen Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has migraine without aura or with typical aura according to criteria of the International Headache Society (IHS)
• Subject has been diagnosed with qi deficiency syndrome and/or blood stasis syndrome in TCM
• Subject has onset of migraine occurring before age 50
• Subject has a history of migraine headaches for at least 1 year
• In recent 3 months, subject has 2 to 8 headache attacks every 4 weeks
• Age ≥ 18 years and ≤ 65 years
• Right-handers
• Subject has signed informed consent

Exclusion Criteria:

• Subject takes painkillers more than 10 days a month for headache attacks
• Subject who was／is in possess of Naoan dripping pills therapy but the treatment is ineffective
• Allergic to Naoan dripping pills
• subject's taken, within 12 weeks before enrollment, migraine prevention drugs drugs such as β-blocker, calcium channel inhibitor，Anti-epileptic drugs，antidepressants or 5-HT receptor blocker
• Alcohol or drug abusers
• Subject suffers from other primary headaches as specified by IHS criteria
• Subject has medical condition such as severe heart disease, stroke, kidney disease, liver disease, hepatic or renal impairment, hematologic disease
• Subject has psychological or mental disorder, Hamilton Anxiety Scale（HAMA）≥7，Hamilton Depression Scale（HAMD）≥7
• Subject has language impairment or cognitive impairment, unable to read, understand or record information in study diaries and questionnaires
• Pregnant or breast feeding subjects
• Subjects with contraindications for undergoing MRI scans (e.g. Claustrophobic, patients with heart pacemaker )

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Naoan dripping pills for migraine; Drug: Naoan dripping pills, Chinese patent medicine，pill. Patients will receive treatment with Naoan dripping pills for 12 weeks, Fenbid can be taken if headache is unbearable Procedure: MRI scanning（fMRI and DTI）	Drug: Naoan dripping pills; Patients will take 20 pills(1000mg) after meal twice a day for 12 weeks, Fenbid can be taken if headache is unbearable, but make sure the records(including attack time, drug dosage, pain intensity and duration) are written down as detailed as possible. Procedure: MRI scanning (fMRI and DTI）
Placebo Comparator: Placebo; Drug: Placebo, pill. Patients will receive treatment with placebo for 12 weeks, Fenbid can be taken if headache is unbearable Procedure: MRI scanning （fMRI and DTI）	Drug: Placebo; Patients will take 20 pills(1000mg) after meal twice a day for 12 weeks, Fenbid can be taken if headache is unbearable, but make sure the records(including attack time, drug dosage, pain intensity and duration) are written down as detailed as possible. Procedure: MRI scanning (fMRI and DTI)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Responder rate	Defined as the percentage of subjects in a treatment group with 50 % or greater reduction in attack frequency during treatment compared with the baseline period	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in functional connectivity assessed by Resting-state fMRI	Investigate the differences in fractional anisotropy of migraine patients compared to healthy volunteers at baseline, and compare the changes of fractional anisotropy after 12 weeks' treatment in two groups	Baseline and 12 weeks
Change in fractional anisotropy (FA) assessed by DTI	Investigate the differences in fractional anisotropy of migraine patients compared to healthy volunteers at baseline, and compare the changes of fractional anisotropy after 12 weeks' treatment in two groups	Baseline and 12 weeks
Duration of migraine attacks	To compare the reduction of duration of migraine attacks after 12 weeks' treatment in two groups	12 weeks and 16 weeks
Intensity of headache	To compare the change of the duration of migraine attacks (mild, moderate, severe) after 12 weeks' treatment in two groups	12 weeks and 16 weeks
Patient reported outcome (PRO) scale of migraine	To compare the change of Patient reported scores after 12 weeks' treatment in two groups	12 weeks and 16 weeks
Number of migraine days per evaluation interval	To compare the reduction of the number of migraine days per evaluation interval after 12 weeks' treatment in two groups	12 weeks and 16 weeks
Drug consumption for symptomatic or acute treatment	To compare the change of drug consumption for symptomatic or acute treatment after 12 weeks' treatment in two groups	12 weeks and 16 weeks

Collaborators and Investigators

• Sponsor: Dongzhimen Hospital, Beijing
• Collaborators: Zhejiang Liaoyuan Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2017
• Primary Completion (Actual): July 4, 2018
• Study Completion (Actual): August 4, 2018

Study Registration Dates

• First Submitted: May 30, 2017
• First Submitted That Met QC Criteria: June 1, 2017
• First Posted (Actual): June 5, 2017

Study Record Updates

• Last Update Posted (Actual): February 19, 2019
• Last Update Submitted That Met QC Criteria: February 17, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Migraine; fMRI; Traditional Chinese Medicine; Randomized Controlled trial; Naoan dripping pills
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: PRO-2016-84-01

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: No
• Studies a U.S. FDA-regulated device product: No