Effect of Ketamine Intranasal Spray in Treatment of Chronic Cluster Headache

Proof of Concept Study for Evaluation of the Effect of Ketamine Intranasal Spray in Treatment of Chronic Cluster Headache

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

Study Overview

• Status: Completed
• Conditions: Cluster Headache
• Intervention / Treatment: Drug: Ketamine

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, DK-2600
    • Danish Headache Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on pain intensity at 15 min (50% reduction)	A 50% or more reduction in pain on a ten-point NRS scale (0: no pain, 10: worst imaginable pain) at T15 from pain intensity at T=0 .	15 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect on pain intensity at 30 min	A 50% or more reduction in pain on a ten-point NRS scale (0: no pain, 10: worst imaginable pain) at T30 from pain intensity at T=0.	30 minutes
Effect on pain intensity at 15 min (25% reduction)	A 25% reduction in pain on a ten-point NRS scale (0: no pain, 10: worst imaginable in) at T15 from pain intensity at T=0.	15 minutes
Proportion of patients achieving NRS less than 4 at 15 minutes	Proportion of patients achieving NRS less than 4 at 15 minutes	15 minutes
Proportion of patients achieving NRS less than 4 at 30 minutes	Proportion of patients achieving NRS less than 4 at 30 minutes	30 minutes
Proportion of patients receiving rescue medication at 15 minutes	Proportion of patients receiving rescue medication at 15 minutes	15 minutes
Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan.	Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan.	180 minutes (entire attack)
Proportion of patients experiencing serious side effects during treatment	Proportion of patients experiencing serious side effects during treatment	one week follow-up.

Collaborators and Investigators

• Sponsor: CCH Pharmaceuticals
• Collaborators: Danish Headache Center

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): May 12, 2020
• Study Completion (Actual): May 25, 2020

Study Registration Dates

• First Submitted: November 25, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (Actual): November 27, 2019

Study Record Updates

• Last Update Posted (Actual): February 24, 2021
• Last Update Submitted That Met QC Criteria: February 23, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• 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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 2019-001260-29

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Do to GDPR rules individual data will not be shared. Group data will be presented in publication. By request by other researcher other data will be presented if the request lines within the out approval from the The Danish Data Protection Agency

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No