Prophylactic Treatment of Episodic Cluster Headache

• ClinicalTrials.gov Identifier: NCT00184587
• Recruitment Status: Completed
• First Posted: September 16, 2005
• Last Update Posted: April 23, 2013
• Sponsor: Norwegian University of Science and Technology
• Collaborator: AstraZeneca
• Information provided by (Responsible Party): Norwegian University of Science and Technology

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Cluster Headache	Drug: candesartan cilexetil; Drug: placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Prophylactic Treatment of Episodic Cluster Headache With an Angiotensin II Receptor Blocker (Candesartan Cilexetil); a Randomized, Placebo Controlled Parallel Study
• Study Start Date: March 2005
• Actual Primary Completion Date: June 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

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 Name: 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

Outcome Measures

Primary Outcome Measures :

1. frequency of attacks per week [ Time Frame: change from 'pseudobaseline' week 1 to week 3 ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

Norway

Norwegian National Headache Centre St.Olavs Hospital

Trondheim, Norway, 7006

Sponsors and Collaborators

Norwegian University of Science and Technology

AstraZeneca

Investigators

• Principal Investigator: Lars J Stovner, PhD; Norwegian National Headache Center St.Olavs Hospital

More Information

Publications of Results:

Tronvik E, Wienecke T, Monstad I, Dahløf C, Bøe 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.

Other 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.

• Responsible Party: Norwegian University of Science and Technology
• ClinicalTrials.gov Identifier: NCT00184587
• Other Study ID Numbers: D2452L0004; 2004-002737-39 ( EudraCT Number ); 045-04 ( Other Identifier: Norwegian National Headache Centre ); 10815 ( Other Identifier: NSD )
• First Posted: September 16, 2005
• Last Update Posted: April 23, 2013
• Last Verified: September 2010

Keywords provided by Norwegian University of Science and Technology:

prophylactic; episodic; cluster; candesartan; angiotensin II receptor blocker; randomized placebo controlled parallel study; headache diary

Additional relevant MeSH terms:

Cluster Headache; Headache; Pain; Neurologic Manifestations; Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Candesartan; Candesartan cilexetil; Angiotensin II; Angiotensin Receptor Antagonists; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Molecular Mechanisms of Pharmacological Action; Vasoconstrictor Agents