Evaluation of Efficacity and Safety of Deep Brain Stimulation (DBS) in Chronic and Treatment-Resistant Cluster Headache(CH)

Study Overview
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Brief Summary
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The aim of this study is to evaluate the efficacy and safety of deep brain stimulation (DBS) in chronic and treatment-resistant CH. Inclusion criteria are: patients with chronic CH (>3years), with daily attack and non response to adequate treatment. Electrodes are implanted stereotactically in the postero-inferior hypothalamus. In this crossover, randomized, placebo-controlled double-blinded study, the efficacy of DBS is evaluated using comparison of two one-month sequences: one with stimulation on and the other with stimulation off (placebo sequence). Efficacy is defined as ≥50% decrease of weekly frequency of CH attacks. After the randomized period, long-term efficacy and safety are evaluated after one year of stimulation in open conditions.

Detailed Description
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Over the past 7 years, deep brain stimulation (DBS) has been used in various centres to treat patients with intractable chronic cluster headache (CH). Results in these non-controlled studies were encouraging but need to be confirmed in controlled conditions. The aim of this study is to evaluate the efficacy and safety of DBS in chronic and treatment-resistant CH, in randomized placebo-controlled conditions. Inclusion criteria are: patients with chronic CH (>3years), with daily attack and non response to adequate treatment (verapamil up 960 mg/d, lithium with plasmatic level 0.6-1 mEq/ ml, and association of both drugs). After induction of local anaesthesia, electrodes are implanted stereotactically in the postero-inferior hypothalamus according to the previously described coordinates, and connected to a sub-cutaneous generator. In this crossover, randomized, placebo-controlled double-blinded study, the efficacy of DBS is evaluated using comparison of two one-month sequences: one with stimulation on and the other with stimulation off (considered as the placebo sequence). Primary efficacy is defined as ≥50% decrease of weekly frequency of CH attacks, compared to a prospective run-in pre-implantation period. Safety and tolerability are clinically and biologically assessed. After the randomized period, long-term efficacy and safety are evaluated after one year of stimulation in open conditions.

Official Title
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Evaluation of Efficacity and Safety of Deep Brain Stimulation (DBS) in Chronic and Treatment-Resistant Cluster Headache(CH)

Conditions
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Cluster Headache

Intervention / Treatment
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* Procedure: setting-up of an electrode in deep brain


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: between 18 and 65 year old suffering from cluster headache since 3 years at least not responding to others treatments such as : verapamil, lithium or both of them Exclusion Criteria: patient with addiction pregnancy or feeding women contraindication to general anesthetic contraindication to MRI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2<br>the sequence of stimulation begins by OFF | Procedure: setting-up of an electrode in deep brain<br>* deep brain stimulation of the postero-inferoir hypothalamus<br>|
| Experimental: 1<br>the sequence of stimulation begins by ON | Procedure: setting-up of an electrode in deep brain<br>* deep brain stimulation of the postero-inferoir hypothalamus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease (≥50% by reference to a prospective pre-implantation run-in period) of the weekly frequency of cluster headache attacks between treatment and placebo one-month sequences. |  | between treatment and placebo one-month sequences. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Intensity of dysautomic dysfunction, acute treatment consumption, quality of life Between treatment and placebo one-month sequences. |  | Between treatment and placebo one-month sequences. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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deep brain stimulation, cluster headache, hypothalamus