Comparison of Propranolol, Flunarizine and Their Combination in Preventing Migraine in Adults in a Tertiary Care Hospital in Bangladesh

NCT07655700 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 59.127.1557.013.19.PG.2026./36
• Study Type: interventional
• Target: 177
• Locations: 1 country
• Sites: 1

Brief Summary

Migraine is a common and disabling neurological condition that affects quality of life, work productivity, and daily functioning. In Bangladesh, migraine is a major health problem, yet access to effective and affordable preventive treatments remains limited. Preventive (prophylactic) treatment is recommended for people who experience frequent migraine attacks in order to reduce the number, severity, and duration of headaches. Propranolol and flunarizine are two commonly used and relatively inexpensive medications for migraine prevention. Both drugs have been shown to reduce migraine frequency when used alone. However, some patients do not respond adequately to a single medication. Using a combination of drugs that work through different mechanisms may improve treatment effectiveness without significantly increasing side effects. There is limited local evidence comparing propranolol, flunarizine, and their combination in migraine prevention, particularly in the Bangladeshi population. This study is designed to compare the effectiveness and safety of propranolol alone, flunarizine alone, and a combination of propranolol and flunarizine in preventing episodic migraine in adults. The main hypothesis is that at least one of these treatment strategies, particularly combination therapy, may be more effective than the others in reducing migraine burden. This is an open-label, parallel-arm, randomized controlled trial conducted at Chittagong Medical College Hospital, Bangladesh. A total of 177 adult patients aged 18 to 55 years who are diagnosed with episodic migraine and experience four or more migraine attacks per month will be enrolled. Participants will be randomly assigned to one of three treatment groups: propranolol, flunarizine, or a combination of both medications. Treatment will be given for 12 weeks, with dose adjustments during the first week and follow-up visits at 6 and 12 weeks. The primary outcome of the study is the reduction in the number of monthly migraine days. Secondary outcomes include the proportion of patients achieving at least a 50% reduction in migraine days, changes in headache severity and duration, improvement in migraine-related disability (measured by the Migraine Disability Assessment Score), patient-reported treatment satisfaction, and the frequency of side effects. The results of this study are expected to provide important local evidence to guide clinicians in selecting effective and affordable migraine preventive treatments and to clarify whether combination therapy offers additional benefits over single-drug therapy in routine clinical practice.

Conditions

Migraine Prophylaxis

Keywords

Migraine Prophylaxis; Randomized Controlled Trial; Combination Therapy; Propranolol; Flunarizine

Outcome Measures

Primary Outcomes (1)

• Change in Monthly Migraine Days

  Monthly Migraine Days refers to the total number of days within a month on which a participant experiences a migraine headache. The change will be measured as the difference between the baseline number of monthly migraine days and the number recorded at the end of the study.

  From baseline to 12 weeks

Secondary Outcomes (6)

• Responder Rate (≥50% reduction in monthly migraine days)

  Baseline to 12 weeks

• Change in Headache Severity (Numeric Rating Scale)

  Baseline, Week 6, and Week 12

• Change in Headache Duration

  Baseline, Week 6, and Week 12

• Change in MIDAS (Migraine Disability Assessment) Score

  Baseline and end of treatment (Week 12)

• Patient Global Evaluation

  End of the treatment Week 12

Study Arms (3)

Propranolol arm

ACTIVE COMPARATOR

Participants randomized to this arm will receive propranolol as the sole prophylactic medication for migraine, administered for a total of 12 weeks. Propranolol will be started at 40 mg daily and increased to 80 mg daily after 7 days

Drug: Propranolol 80 mg

Flunarizine arm

ACTIVE COMPARATOR

Participants randomized to this arm will receive flunarizine as the sole prophylactic medication for migraine, administered for a total of 12 weeks. Flunarizine will be started at 5 mg daily and increased to 10 mg daily after 7 days

Drug: Flunarizine 10 mg

Combination arm

ACTIVE COMPARATOR

Participants randomized to this arm will receive a combination of propranolol and flunarizine for migraine prophylaxis, administered for a total of 12 weeks. Treatment will be started at propranolol 40 mg daily plus flunarizine 5 mg daily. After 7 days, the propranolol dose will be maintained at 40 mg daily while the flunarizine dose will be increased to 10 mg daily.

Drug: Propranolol 40 mg + Flunarizine 10mg

Interventions

Propranolol 80 mg DRUG

Participants randomized to propranolol arm will receive propranolol as the sole prophylactic medication for migraine, administered for a total of 12 weeks. Propranolol will be started at 40 mg daily and increased to 80 mg daily after 7 days

Propranolol arm

Flunarizine 10 mg DRUG

Participants randomized to flunarizine arm will receive flunarizine as the sole prophylactic medication for migraine, administered for a total of 12 weeks. Flunarizine will be started at 5 mg daily and increased to 10 mg daily after 7 days

Flunarizine arm

Propranolol 40 mg + Flunarizine 10mg DRUG

Participants randomized to combination arm will receive a combination of propranolol and flunarizine for migraine prophylaxis, administered for a total of 12 weeks. Treatment will be started at propranolol 40 mg daily plus flunarizine 5 mg daily. After 7 days, the propranolol dose will be maintained at 40 mg daily while the flunarizine dose will be increased to 10 mg daily.

Combination arm

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants aged 18 to 55 years.
• Diagnosis of episodic migraine, defined according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria.
• Participants experiencing 4 or more migraine attacks per month.
• Willingness to provide written informed consent to participate in the study.

You may not qualify if:

• Comorbidities:
• Presence of other primary headache disorders, chronic migraine, hemiplegic migraine, basilar migraine or any secondary headache disorder.
• Known serious underlying systemic diseases including Cardiac disease (Heart failure, Heart Block, Arrhythmia), Renal dysfunction, Liver dysfunction, Pulmonary disease (Asthma, COPD), Peripheral vascular disease, Extrapyramidal disease (Parkinson disease, Chorea, Dystonia).
• Pregnancy or breastfeeding.
• Psychiatric illness (Depression, Psychosis, Obsessive compulsive disorder).
• Medications:
• Received migraine prophylactic medication within 60 days prior to screening.
• Use of specific contraindicated medications, including beta-blockers or calcium channel blockers, except as part of the study treatments.
• Non-compliance:
• Inability or unwillingness to comply with study protocols, including maintaining a headache diary or attending follow-up visits.
• History of Allergies:
• Known hypersensitivity to propranolol, flunarizine
• Substance Use:
• Current substance abuse

Sponsors & Collaborators

• Chittagong Medical College: lead

Study Sites (1)

Chittagong Medical College

Chittagong, 4203, Bangladesh

Location

Related Publications (7)

• Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018 Jan;38(1):1-211. doi: 10.1177/0333102417738202. No abstract available.

  PMID: 29368949 BACKGROUND

• Ahmed, K.G.U., Mahmud, R., Islam, M.R., Chowdhury, A.H., Alam, I., Rassel, M.A. and Monayem, F.B., 2019. Migraine Headache: A Bangladesh Perspective. Bangladesh Journal of Neuroscience, 35(1), pp.1-9.

  BACKGROUND

• Bordini CA, Arruda MA, Ciciarelli MC, Speciali JG. Propranolol vs flunarizine vs flunarizine plus propranolol in migraine without aura prophylaxis. A double-blind trial. Arq Neuropsiquiatr. 1997 Sep;55(3B):536-41. doi: 10.1590/s0004-282x1997000400003.

  PMID: 9629401 BACKGROUND

• Raybarman, C., 2016. The efficacy of combined low-doses of propranolol and flunarizine in episodic migraine. East Journal of Medicine, 21(2), pp.75-78.

  BACKGROUND

• Hasan, M.K., Khan, I., Salam, T. and Sharmin, M., 2019. The current status of treatment among migraine patients in Bangladesh. JMSCR, 07(12), pp.823-828.

  BACKGROUND

• Dixit, M., Singh, A.K., Nim, D.K. and Chaurasia, R.C., 2024. Is the combination of propranolol and flunarizine better than propranolol, flunarizine and amitriptyline alone in prophylaxis of migraine? An observational study at a tertiary care centre of North India. Int. J. Basic. Clin. Pharmacol, 13, pp.884-890.

  BACKGROUND

• Alam, M.S., Chowdhury, A.M.K., Mamun, S., Rahman, T., Waddadar, S., Das, P., Khan, M.A., Akter, N., Tayeb, M. and Hassanuzzaman, M., 2024. Comparative Study of Flunarizine versus Propranolol in the Prophylaxis of Migraine. Chattagram Maa-O-Shishu Hospital Medical College Journal, 23(2), pp.24-28.

  BACKGROUND

MeSH Terms

Interventions

Propranolol; Flunarizine

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Mohammad Shaifuddin Shourav, MBBS

CONTACT

8801832287641; shaifuddinshourav@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident, Phase B, Neurology

Model Details: This is an open-label, parallel-arm randomized controlled trial with three treatment groups (Propranolol, Flunarizine, and Combination), each receiving its assigned intervention for 12 weeks with no crossover between arms. Participants will be randomly allocated in a 1:1:1 ratio (59 participants per arm, total n=177) using a software-generated block randomization scheme with a block size of six, to ensure balanced distribution across the three groups. Allocation concealment will be maintained using sealed opaque envelopes. As the study is open-label, both investigators and participants will be aware of treatment assignment after allocation; there is no blinding.

Study Record Dates

• First Submitted: June 12, 2026
• First Posted: June 18, 2026
• Study Start: July 1, 2026
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

BA (1)