Effect of Ketamine Intranasal Spray in Treatment of Chronic Cluster Headache

• ClinicalTrials.gov Identifier: NCT04179266
• Recruitment Status: Completed
• First Posted: November 27, 2019
• Last Update Posted: February 24, 2021
• Sponsor: CCH Pharmaceuticals
• Collaborator: Danish Headache Center
• Information provided by (Responsible Party): CCH Pharmaceuticals

Tracking Information

• First Submitted Date: November 25, 2019
• First Posted Date: November 27, 2019
• Last Update Posted Date: February 24, 2021
• Actual Study Start Date: November 20, 2019
• Actual Primary Completion Date: May 12, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2019)

Effect on pain intensity at 15 min (50% reduction) [ Time Frame: 15 minutes ]

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 .

Original Primary Outcome Measures (submitted: November 26, 2019)

Effect on pain intensity at 15 min (50% reduction) [ Time Frame: 15 min ]

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 .

Current Secondary Outcome Measures (submitted: November 26, 2019)

• Effect on pain intensity at 30 min [ Time Frame: 30 minutes ]
  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.
• Effect on pain intensity at 15 min (25% reduction) [ Time Frame: 15 minutes ]
  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.
• Proportion of patients achieving NRS less than 4 at 15 minutes [ Time Frame: 15 minutes ]
  Proportion of patients achieving NRS less than 4 at 15 minutes
• Proportion of patients achieving NRS less than 4 at 30 minutes [ Time Frame: 30 minutes ]
  Proportion of patients achieving NRS less than 4 at 30 minutes
• Proportion of patients receiving rescue medication at 15 minutes [ Time Frame: 15 minutes ]
  Proportion of patients receiving rescue medication at 15 minutes
• Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan. [ Time Frame: 180 minutes (entire attack) ]
  Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan.
• Proportion of patients experiencing serious side effects during treatment [ Time Frame: one week follow-up. ]
  Proportion of patients experiencing serious side effects during treatment

Original Secondary Outcome Measures (submitted: November 26, 2019)

• Effect on pain intensity at 30 min [ Time Frame: 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.
• Effect on pain intensity at 15 min (25% reduction) [ Time Frame: 15 min ]
  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.
• Proportion of patients achieving NRS less than 4 at 15 minutes [ Time Frame: 15 min ]
  Proportion of patients achieving NRS less than 4 at 15 minutes
• Proportion of patients achieving NRS less than 4 at 30 minutes [ Time Frame: 30 min ]
  Proportion of patients achieving NRS less than 4 at 30 minutes
• Proportion of patients receiving rescue medication at 15 minutes [ Time Frame: 15 min ]
  Proportion of patients receiving rescue medication at 15 minutes
• Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan. [ Time Frame: 180 min (entire attack) ]
  Proportion of patients preferring ketamine treatment compared to oxygen or injectable sumatriptan.
• Proportion of patients experiencing serious side effects during treatment [ Time Frame: one week follow-up. ]
  Proportion of patients experiencing serious side effects during treatment

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

open label - proof of concept study

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Cluster Headache

Intervention

Drug: Ketamine

One Cluster headache attack is treated with intranasal ketamine

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 23, 2021): 23
• Original Estimated Enrollment (submitted: November 26, 2019): 20
• Actual Study Completion Date: May 25, 2020
• Actual Primary Completion Date: May 12, 2020 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Denmark

Administrative Information

• NCT Number: NCT04179266
• Other Study ID Numbers: 2019-001260-29
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No
• 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

• Current Responsible Party: CCH Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: CCH Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Danish Headache Center
• Investigators: Not Provided
• PRS Account: CCH Pharmaceuticals
• Verification Date: February 2021