Clinical trial NCT04179266: Effect of Ketamine Intranasal Spray in Treatment of Chronic Cluster Headache
Official title: Proof of Concept Study for Evaluation of the Effect of Ketamine Intranasal Spray in Treatment of Chronic Cluster Headache
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Cluster Headache
Lead sponsor: CCH Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Danish Headache Center
First posted: 2019-11-27
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label - proof of concept study
Primary purpose: TREATMENT

Brief summary: Ketamine has been used clinically IV in a very safe manner by a very small number of clinicians, to treat migraines and CH, and various other rarer pain disorders, including mixed headache and neuropathic pain clinical syndromes. In 5 cases taken from Krusz J.C. headache clinic data in Dallas, Texas US, an intranasal spray of ketamine aqueous solution of 100 µL in one nostril were dosed in treatment of patients with refractory chronic cluster headache as an alternative to IV-treatment (data not published).The net conclusion, at this point, is that intranasal ketamine is a legitimate pharmacologic treatment and is safe and has in one case series proven effective for CH rescue.

The CCH patients will be dosed with an intranasal spray containing 172.5 mg ketamine hydrochloride (150 mg ketamine base) per ml in an aqueous solution. The individual dosing includes 15 mg ketamine in an intranasal sprayed volume of 100 µL given in one nose nostril under supervision of a nurse. The treatment is initiated at T0 under a CH attack when the headache pain exceeds NRS = 6 on an NRS pain scale. The first intranasal dose of 15 mg is given at time 0 and at time intervals of 6 minutes. At 15 minutes after 3 doses (45 mg) it is decided to evaluate whether the patient is sufficiently pain relieved (e.g. NRS \< 4) or wants to receive rescue medications instead or if pain is not sufficiently relieved wants to continue until 5 dosing's (75 mg) are received at timepoints T24. The final evaluation of the treatment is performed at T30. Participants are followed up after 1-2 weeks by telehone


Eligibility criteria: Inclusion Criteria:

* Signed informed consent
* Age between 18 and 60 years
* Diagnose: Chronic cluster headache according to ICHD-3 criteria (1)
* Body weight ≥50 kg and BMI ≤30

Exclusion Criteria:

* Conditions that result in the participant being unable to complete the experiment
* Medical history with elevated intraocular pressure (e.g. glaucoma)
* Medical history with severe heart or liver disease
* Aneurysmal vascular disease or arteriovenous malformations
* Medical history with severe neurological disease except of headache
* BP measured at baseline before CH attack (Systolic\> 140 mmHg or / and diastolic blood pressure\> 90 mm Hg)
* Medical history with severe depression or psychosis
* A previous history of drug abuse
* Consumption of illegal drugs within the last 6 months
* Medical history of nasal abnormality or dysfunction (e.g. rhinitis)
* High disposition for larynges or apnea
* Positive pregnancy test before treatment and breastfeeding
* Known hypersensitivity to ketamine

Primary outcomes:
measure: Effect on pain intensity at 15 min (50% reduction)
timeFrame: 15 minutes
Secondary outcomes:
measure: Effect on pain intensity at 30 min
timeFrame: 30 minutes
measure: Effect on pain intensity at 15 min (25% reduction)
timeFrame: 15 minutes
measure: Proportion of patients achieving NRS less than 4 at 15 minutes
timeFrame: 15 minutes
measure: Proportion of patients achieving NRS less than 4 at 30 minutes
timeFrame: 30 minutes
measure: Proportion of patients receiving rescue medication at 15 minutes
timeFrame: 15 minutes
measure: Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan.
timeFrame: 180 minutes (entire attack)
measure: Proportion of patients experiencing serious side effects during treatment
timeFrame: one week follow-up.
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Danish Headache Center
Study officials:
References: