Candesartan for Migraine Prevention: (CandMig-3)

Candesartan for Migraine Prevention: A Multicentre, Binational, Triple Blind, Placebo Controlled, Parallel Group Study of Two Doses of Candesartan (8 and 16 mg)

The main objective of this study is to see whether the favorable preventative effect of candesartan 16 mg per day in episodic migraine, that was found previously in two smaller randomized controlled cross-over studies, can be confirmed in a larger, multicenter, randomized controlled parallel group study. In addition it will be investigated whether 1) also a smaller dose of 8 mg is effective, and 2) whether the favorable side effect profile, seen in previous studies, can be confirmed, and whether it is even better with the smaller dose.

Study Overview

• Status: Active, not recruiting
• Conditions: Migraine
• Intervention / Treatment: Drug: Candesartan Oral Tablet 8 mg; Drug: Candesartan Oral Tablet 16 mg; Drug: Placebo oral tablet

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Erling Tronvik, md prof; Phone Number: +47 40458528; Email: erling.tronvik@ntnu.no
• Study Contact Backup: Name: Lise Rystad Øie, phd; Email: lise.r.oie@ntnu.no

Study Locations

• Estonia
  • Tartu, Estonia
    • Tartu University Clinics
• Norway
  • Bergen, Norway
    • Haukeland University Hospital
  • Bodø, Norway
    • Nordland Hospital
  • Kristiansand, Norway
    • Sørlandet Hospital
  • Lørenskog, Norway
    • Akershus University Hospital AHUS
  • Molde, Norway
    • Møre and Romsdal Hospital Molde
  • Oslo, Norway
    • Ullevål University Hospital
  • Oslo, Norway
    • Rikshospitalet University Hospital
  • Tromsø, Norway
    • University Hospital of North Norway
  • Trondheim, Norway
    • St Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 64 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Signed informed consent
2. Episodic migraine with or without aura according to ICHD-3 criteria
3. At inclusion, patients should retrospectively have from 2 to 8 migraine attacks per month during the last 3 months. This frequency must be confirmed in the headache diary before randomization to treatment.
4. Debut of migraine at least one year prior to inclusion
5. Start of migraine before age 50 years
6. No use of other migraine prophylactics during the study
7. For women of child-bearing potential, use of highly effective contraception.

Exclusion Criteria:

1. Interval headache not distinguishable from migraine;
2. Chronic migraine, chronic tension-type headache, medication overuse headache or other headache occurring on ≥ 15 days/month
3. Pregnancy, planning to get pregnant, inability to use contraceptives, lactating
4. Clinical information on or signs of cholestasis or decreased hepatic or renal function. If in doubt, relevant blood tests should be performed
5. High degree of comorbidity and/or frailty associated with reduced life expectancy or high likelihood of hospitalization, at the discretion of the investigator
6. Hypersensitivity to candesartan
7. History of angioneurotic oedema
8. Current use of antihypertensive medication
9. Current use of potassium supplements
10. Current use of spironolactone
11. Primary hyperaldosteronism (Conn's syndrome)
12. Significant psychiatric illness
13. Use of medicines for migraine prophylaxis less than 4 weeks, or of botulinum toxin less than 16 weeks, prior to start of study
14. Having tried ≥ 3 prophylactic drugs against migraine during the last 10 years
15. Previous use of candesartan
16. Requiring detoxification from acute medication (triptans, opioids)
17. Consistently failing to respond to any acute migraine medication
18. Alcohol or illicit drug dependence.
19. Inability to understand study procedures and to comply with them for the entire length of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group	Drug: Placebo oral tablet; 1 over-encapsulated tablet once daily, containing placebo, for 12 weeks (84 days).
Experimental: Candesartan 8 mg	Drug: Candesartan Oral Tablet 8 mg; 1 over-encapsulated tablet once daily, containing candesartan 8 mg, for 12 weeks (84 days).
Experimental: Candesartan 16 mg	Drug: Candesartan Oral Tablet 16 mg; 1 over-encapsulated tablet once daily, containing candesartan 16 mg, for 12 weeks (84 days).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in number of migraine days per 4 weeks, from baseline	participants will fill in a headache diary during 20 weeks treatment	20 weeks plus final visit 1 week after treatment

Collaborators and Investigators

• Sponsor: St. Olavs Hospital
• Collaborators: Ullevaal University Hospital; University Hospital of North Norway; Norwegian University of Science and Technology; Haukeland University Hospital; Sorlandet Hospital HF; Rikshospitalet University Hospital; University Hospital, Akershus; Nordlandssykehuset HF; Molde Hospital; Tartu University Hospital
• Investigators: Study Director: Christian Samsonsen, md phd, St Olavs Hospital, Dept Neurology & Clinical Neurophysiology; Study Director: Jorunn L Helbostad, prof, Norwegian University of Science and Technology, Fac MH, Dept INB; Principal Investigator: Erling Tronvik, md prof, Norwegian University of Science and Technology, Fac MH, Dept INB

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2020
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: September 28, 2020
• First Submitted That Met QC Criteria: October 2, 2020
• First Posted (Actual): October 5, 2020

Study Record Updates

• Last Update Posted (Actual): April 5, 2024
• Last Update Submitted That Met QC Criteria: April 4, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Prevention and Control; Candesartan
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Candesartan; Candesartan cilexetil
• Other Study ID Numbers: 63527; 2019-003386-18 (EudraCT Number); NFR 288699. (Other Grant/Funding Number: Research Council of Norway)

Drug and device information, study documents

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