Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches

Chronic daily headaches (CDH) poses a significant burden on patients, healthcare systems and the society. Intravenous (IV) ketamine infusion, an intervention that is widely available and scalable, can treat CDH by reversing receptor-mediated sensitization. This study is a multicenter, placebo-controlled, parallel group randomized trial with blinding of participants and observers with the goal of comprehensively assessing the effect of high-dose IV ketamine infusion (1 mg.kg-1.h-1 for six hours) on the frequency and intensity of headaches, mood, activity, sleep, quality of life and safety of ketamine for three months after the interventions. Use of validated questionnaires, wearable technology, a research team that includes investigators with expertise in studying ketamine and in evaluating treatments for CDH and pain syndromes are some of the unique features of this project. Our study aims to prospectively assess the efficacy and safety of high-dose intravenous ketamine infusions compared to saline infusions in participants with CDH syndrome.

NCT Number	NCT05306899
Lead Sponsor	University Health Network, Toronto Collaborators: The Canadian Pain Society, Pfizer
Conditions	Chronic Daily Headache
Enrollment	56 participants
Start Date	2022-06-01
Primary Completion	2027-02-01 (estimated)
Study Completion	2027-06-01 (estimated)
Updated on ClinicalTrials.gov	2026-06-08