Prophylactic Treatment of Episodic Cluster Headache

Prophylactic Treatment of Episodic Cluster Headache With an Angiotensin II Receptor Blocker (Candesartan Cilexetil); a Randomized, Placebo Controlled Parallel Study

The purpose of this study is to determine whether candesartan cilexetil are effective prophylactic treatment of episodic Cluster headache

Study Overview

• Status: Completed
• Conditions: Cluster Headache
• Intervention / Treatment: Drug: placebo; Drug: candesartan cilexetil

Detailed Description

Cluster headache is an unilateral headache with periodic attacks, that usually lasts for 6 to 12 weeks. The pain is usually unbearable. The attacks are treated with injections of sumatriptan (migraine medication)and inhalation of oxygen.

The most common prophylactics today has limited effect and a risk of side effects.

Candesartan has in one study shown a clinically significant effect in migraine prophylaxis.

The angiotensin II receptor blocker, candesartan is well tolerated with side-effects not significantly different from placebo and with few drug interactions. We therefore wish to investigate the prophylactic effect in treatment of cluster in headache patients.

This will be a multicenter, double-blind, randomized, parallel study where the prophylactic effect of candesartan is compared to placebo in a period of 3 weeks. First week 16 mg and the following 2 weeks 32 mg.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Norway
  • Trondheim, Norway, 7006
    • Norwegian National Headache Centre St.Olavs Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The episodic cluster headache must be diagnosed according to the IHS classification. Had at least one episode with cluster headache before inclusion. Previously had at least one cluster headache episode lasting one month or more. At the time of inclusion, the cluster headache period shall not have lasted more than 3 weeks

Exclusion Criteria:

• Pregnancy, nursing, decreased hepatic og renal function, psychiatric illness, cardiac problems, hypersensitivity to candesartan, previous serious allergic reaction to medication, chronic cluster headache, drug/alcohol abuse, use of antipsychotic,antidepressants, lithium or other prophylactic treatment less than one month prior to inclusion, systolic blood pressure below 110 mmHg, use of other hypertensive medication, use og other specific attack medication than sumatriptan injection or oxygen 7-10l/min and inability to change medication, use of other triptans than sumatriptan during the study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: candesartan; candesartan cilexetil 16 mg (one tablet/day) in week 1 and 32 mg (2 tablets/day) in week 3, provided for the study by AstraZeneca	Drug: candesartan cilexetil; Other Names: angiotensin II receptor blocker
Placebo Comparator: placebo; placebo one tablet/day in week 1 and 2 tablets/day in week 3, provided for the study by AstraZeneca. Same size, weight, taste and appearance as experimental drug	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
frequency of attacks per week	change from 'pseudobaseline' week 1 to week 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
level of disability	5-point scale; 0= no disability, 1= mild, 2= moderate, 3= severe, 4= unbearable	change from 'pseudobaseline' week 1 to week 3
duration of attacks		change from 'pseudobaseline' week 1 to week 3
hours with cluster headache		change from 'pseudobaseline' week 1 to week 3
days with cluster headache		change from 'pseudobaseline' week 1 to week 3
occurrence of autonomic symptoms		change from 'pseudobaseline' week 1 to week 3
number of treatments with sumatriptan or oxygen		change from 'pseudobaseline' week 1 to week 3
patient satisfaction with treatment	scale from 1 to 10 with 1= very poor effect and 10= very good effect	change from 'pseudobaseline' week 1 to week 3
headache severity index	product of level of disability and duration of attacks	change from baseline to 1 week and 3 week
candesartan-responders	patients with a 50% or more reduction in attack frequency in week 3 than in week 1	3 weeks
placebo-responders	patients with a 50% or more reduction in attack frequency in week 3 than in week 1	3 weeks

Collaborators and Investigators

• Sponsor: Norwegian University of Science and Technology
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: Lars J Stovner, PhD, Norwegian National Headache Center St.Olavs Hospital

Publications and helpful links

General Publications

• Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G. Prophylactic treatment of migraine with an angiotensin II receptor blocker: a randomized controlled trial. JAMA. 2003 Jan 1;289(1):65-9. doi: 10.1001/jama.289.1.65.
• Tronvik E, Wienecke T, Monstad I, Dahlof C, Boe MG, Tjensvoll AB, Salvesen R, Zwart JA, Jansson SO, Stovner LJ. Randomised trial on episodic cluster headache with an angiotensin II receptor blocker. Cephalalgia. 2013 Sep;33(12):1026-34. doi: 10.1177/0333102413484989. Epub 2013 Apr 18.

Study record dates

Study Major Dates

• Study Start: March 1, 2005
• Primary Completion (Actual): June 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: September 13, 2005
• First Submitted That Met QC Criteria: September 13, 2005
• First Posted (Estimate): September 16, 2005

Study Record Updates

• Last Update Posted (Estimate): April 23, 2013
• Last Update Submitted That Met QC Criteria: April 22, 2013
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Keywords: prophylactic; candesartan; cluster; episodic; angiotensin II receptor blocker; randomized placebo controlled parallel study; headache diary
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Headache Disorders, Primary; Headache Disorders; Trigeminal Autonomic Cephalalgias; Headache; Cluster Headache; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Vasoconstrictor Agents; Candesartan; Candesartan cilexetil; Angiotensin II; Angiotensin Receptor Antagonists
• Other Study ID Numbers: D2452L0004; 10815 (Other Identifier: Fred Hutch/University of Washington Cancer Consortium); 2004-002737-39 (EudraCT Number); 045-04 (Other Identifier: Norwegian National Headache Centre)