Effect of Nicotinic Acid as Add on Therapy in Patients Receiving β Blocker for Prophylaxis of Moderate to Severe Migraine

NCT ID: NCT05846373

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-25
• Study Completion Date: 2024-01-10

Brief Summary

This is a prospective single center, randomized, double-blind, 3 arm placebo-controlled study in subjects with migraine headache requiring prophylactic treatment. The patients will be randomized to receive Nicotinic Acid Extended-release tablet 500 mg or 1000 mg or placebo for 12 weeks. The safety and efficacy outcome measures will be assessed at baseline and 12 weeks.

Detailed Description

Migraine is "a common episodic neurological disorder with complex pathophysiology that manifests as recurrent attacks of typically throbbing and unilateral, often severe headache with certain associated features such as nausea, phonophobia, and photophobia". Worldwide, estimated prevalence was 13.8% to 15%. Quality of life of a migraine patient is extremely low and migraine badly hampers one's physical, emotional, and social efficiency and disrupt familial, social and professional relationships. Diagnosis is solely clinical depending on characteristics of headache and associated symptoms. Neuroimaging can be done only when exclusion of another cause of headache is needed.

Exact etiology and pathophysiology of migraine is unknown and multifactorial. There are several hypotheses of migraine pain generation. Local dilatation of intracranial and extracerebral vessels activate trigeminal nerve surrounding cerebral and meningeal vasculature. Migraine pain starts from the activation of trigeminovascular system. Afferent fibers innervating cerebral and meningeal vessels project to central nervous system and releases vasoactive peptides and inflammatory mediators. Some important mediators like Calcitonin gene related peptide (CGRP), NO, Substance P play role in inflammation and vasodilatation. Then sensitization and discharge of thalamic neuron and subsequent projection to sensory cortical neurons occurs. Thus, pain perception is received in migraine.

In studies, elevated levels of C reactive protein (CRP) and Transforming growth factor β (TGF-β) provides evidence of neuroinflammation. In migraine, impairment of cerebral mitochondrial energy metabolism and oxidative stress occurs. As a result, abnormalities in cerebral vasculature results in Cortical Spreading Depression (CSD).

Niacin, which is known as nicotinic acid or Vitamin B3 is the precursor of Nicotinamide Adenine Dinucleotide (NAD) or Nicotinamide Adenine Dinucleotide Phosphate (NADP). From dietary tryptophan, through kynurenine pathway, NAD is produced, and rest 1% tryptophan is catabolized to form serotonin (5- hydroxytryptamine/ 5-HT). Migraine is a serotonin deficient condition. It has been estimated that, dietary intake of Niacin is low in migraine patients.

Niacin supplementation provides enough NAD to inhibit Kynurenine pathway and accelerate production of 5-HT from tryptophan. Serotonin acting on 5-HT1 receptor, causes vasoconstriction. It may activate nerve endings in cerebral microcirculation and sensitize them to vasodilatory kinins. Serotonin also inhibits synthesis, release of NO, glutamate, Calcitonin gene-related peptide (CGRP). As a result, inhibition of afferent pain transmission and prevention of neuroinflammation occurs. Niacin also reduces inflammation evidenced by decrease level of pro inflammatory cytokines like IL-6, IL-1β, TNF α, high-sensitivity C-reactive protein (hs-CRP). Increasing level of Niacin also improves brain energy deficiency, and has potent antioxidant properties, which may be helpful in migraine prevention. However, more prospective investigations are necessary to validate niacin's preventive effect on migraine.

Conditions

Migraine Prophylaxis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Nicotinic Acid Extended-release tablet 500 mg arm

This arm includes 22 Migraine patients receiving beta blocker

Group Type: ACTIVE_COMPARATOR

Nicotinic Acid 500 MG Extended Release Oral Tablet

Intervention Type: DRUG

Nicotinic acid 500 mg for 12 weeks

Nicotinic Acid Extended-release tablet 1000 mg arm

This arm includes 22 Migraine patients receiving beta blocker

Group Type: ACTIVE_COMPARATOR

Nicotinic Acid 1000 MG Extended Release Oral Tablet

Intervention Type: DRUG

Nicotinic acid 1000 mg per day for 11 weeks, titrated from 500 mg/day for 1 week

Control arm

This arm includes 22 Migraine patients receiving beta blocker

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo 1000 mg per day for 11 weeks, titrated from 500 mg/day for 1 week

Interventions

Nicotinic Acid 500 MG Extended Release Oral Tablet

Nicotinic acid 500 mg for 12 weeks

Intervention Type: DRUG

Nicotinic Acid 1000 MG Extended Release Oral Tablet

Nicotinic acid 1000 mg per day for 11 weeks, titrated from 500 mg/day for 1 week

Intervention Type: DRUG

Placebo

Placebo 1000 mg per day for 11 weeks, titrated from 500 mg/day for 1 week

Intervention Type: OTHER

Other Intervention Names

Niacin; Niacin

Eligibility Criteria

Inclusion Criteria

1. Patients suffering from migraine with or without aura according to International ICHD 3 criteria

2. Patients with 4-15 qualified migraine attacks per month during the four weeks of the Baseline Phase

3. History of headache for at least 1 year

4. Age at onset of migraine should be less than 50 years

5. Headache intensity: Moderate to severe (Visual analogue scale score at least 3)

6. Consuming one β Blocker as prophylaxis

Exclusion Criteria

1. Pregnancy and lactation

2. Known case of any hepatic, psychiatric diseases except depression, diabetes mellitus (DM), gout, peptic ulcer disease

3. Known hypersensitivity to niacin

4. Consumption of certain drugs Lipid lowering agents Antiplatelet and Anticoagulants Antihypertensive medications Alcohol or other abusive drugs

5. Plasma Nicotinic acid level > 8.45 µg/mL

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

OTHER

Sponsor Role: lead

Responsible Party

Hudia Ta-din

MBBS

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

BSMMU

Dhaka, , Bangladesh

Countries

Bangladesh

Other Identifiers

BSMMU/2022/11548

Identifier Type: -

Identifier Source: org_study_id