Ketamine infusions compared with saline for chronic daily headache
Tests ketamine given through a vein against saline in adults with chronic daily headache.
Plain-language title generated from the registry record
Registry title: Multi-center RCT of IV Ketamine Efficacy and Safety in Chronic Daily Headaches
Key facts
- Where
- Toronto, CanadaSee the 2 sites
- Phase
- Phase 3
AI summary: who the study is looking for
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with chronic daily headaches who have normal liver and kidney tests. It compares IV ketamine with saline infusions.
- Age
- 18 to 75 years
- Sex
- All sexes can join.
- Disease stage
- Chronic daily headache diagnosed before enrolment: headache episodes lasting 4 or more hours, on 15 or more days a month, for 3 or more months.
- Earlier treatment
- Cannot have used a CGRP antagonist in the 1 month, or Onabotulinum-toxin A in the 3 months, before the infusion.
- Biomarker or test result
- Normal liver and kidney function tests.
Main reasons for not taking part
- Pregnant or breastfeeding
- Existing kidney or liver impairment
- Chronic use of benzodiazepine or antipsychotic medication
- History of stroke or other cerebrovascular event
- Active PTSD or substance use disorder
Read by machine on 12 November 2026.
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, CanadaContact: Emad Al AzaziTaking people
- Women's College HospitalToronto, CanadaContact: Didem BozakTaking 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?
Contact the study team: see the registry record → Contacts and Locations
Print a page for my doctorTrial 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.