Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches
Key facts
- Where
- Toronto, CanadaSee the 2 sites
- Phase
- Phase 3
Could this be for you?
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- Are you between 18 and 75 years old?
Source: NCT05306899, who can take part
Where in Canada
- Toronto Western HospitalToronto, CanadaTaking people
- Women's College HospitalToronto, CanadaTaking people
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- University Health Network, Toronto
- Trial code
- NCT05306899
- Record updated
- 8 June 2026
- Original description
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.Read full original descriptionShow less
A Multi-center Randomized Controlled Trial of Efficacy and Safety of Intravenous Ketamine for Chronic Daily Headaches: The KetHead Study
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.
Inclusion: 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.
Exclusion: Chronic benzodiazepine or antipsychotic medication use; Concomitant use of strong CYP2B6 or CYP2C8 inhibitor; CGRP antagonist use in 1 month or Onabotulinum-toxin A 3 months before infusion; Patients taking opioid medications with daily Oral Morphine Equivalents ≥80 mg; Pre-existing renal impairment; Pre-existing liver impairment; History of cerebrovascular event; Significant and untreated hypertension or severe cardiac condition; Allergy or intolerance to ketamine; Active diagnosis of Post-Traumatic Stress Disorder (PTSD); Active diagnosis of Substance Use Disorder; Pregnant or breastfeeding patients; Hypothyroidism; Glaucoma; Pheochromocytoma; Any significant cognitive or language barriers that impede participation.