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

What this study is about

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.

Who can join (things the study team will check)

✅ You may be able to join if…

• Age 18-75 years
• CDH diagnosis preceding trial enrollment with headache episodes lasting for 4 or more hours occurring on 15 or more days in a month for 3 or more months (International Headache Society-IHS criteria)
• Normal liver and kidney function tests

🚫 You may not be able to join if…

• Pregnant or breastfeeding patients
• Pre-existing renal impairment
• Pre-existing liver impairment
• Chronic benzodiazepine or antipsychotic medication use
• History of cerebrovascular event
• Significant and untreated hypertension or severe cardiac condition
• Hypothyroidism
• Glaucoma
• Concomitant use of strong CYP2B6 or CYP2C8 inhibitor
• Allergy or intolerance to ketamine
• Pheochromocytoma
• Any significant cognitive or language barriers that impede participation
• CGRP antagonist use in 1 month or Onabotulinum-toxin A 3 months before infusion
• Active diagnosis of Post-Traumatic Stress Disorder (PTSD)
• Active diagnosis of Substance Use Disorder
• Patients taking opioid medications with daily Oral Morphine Equivalents ≥80 mg

Where this trial is running

• Women's College Hospital, Toronto, Ontario, Canada
• Toronto Western Hospital, Toronto, Ontario, Canada

Who to contact

Emad Al Azazi · +1 (416) 603 5800 · KetHead@uhn.ca

It's completely normal to call and ask questions before deciding anything. Mention the study ID: NCT05306899.