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

ConditionChronic Daily Headache
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18-75
SponsorUniversity Health Network, Toronto

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

Pregnant or breastfeeding patients

Pre-existing renal impairment

Pre-existing liver impairment

Chronic benzodiazepine or antipsychotic medication use

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ketamine

    Drug

    Bolus of IV Ketamine 1 mg.kg-1 (= 0.1 ml.kg-1) followed by Infusion of Ketamine 1 mg.kg-1.hour-1 (= 0.5 mL.kg-1.hour-1) for 6 hours. All patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events.

  • 0.9% Saline

    Other intervention

    Bolus of IV Saline 0.9% of 0.1 ml.kg-1 followed by Infusion of Saline 0.9% of 0.5 mL.kg-1.hour-1 for 6 hours. All patients will receive IV midazolam 0.04 mg.kg-1 (maximum 3 mg) and subsequently 0.01-0.02 mg.kg-1 every hour to keep participants in a sedated but arousable state (Ramsay Sedation Scale score 3 or 4) to blind the participants and assessors to group allocation. Ondansetron 8 mg and 8 mg of dexamethasone will be administered to prevent nausea, 5000 units of heparin will be given subcutaneously to prevent thrombo-embolic events.

Treatment groups

56 Participants
are divided into 2 treatment groups
Group A: Ketamine infusionActive comparator 1 intervention
Group B: Placebo infusionPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Difference in headache days between the 2 groups

Between-group difference in the number of headache days in the first 4 weeks after the infusion. (Defined as a day in which the headache lasts 4 or more hours, or a headache of any duration for which abortive treatment (anti-inflammatories, triptans, ergot derivatives, opioids) are taken. Patients will be asked to keep track of their headache days in a diary)

Time frame
At 4 weeks

Secondary outcomes

1

Impact of ketamine on headache intensity after infusion

Impact of ketamine on headache intensity at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, using Numerical Rating Scale (0-10)

Time frame
At 1 month, 2 months and 3 months
2

Impact of ketamine on headache frequency after infusion

Impact of ketamine on headache frequency at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, as number of headache episodes per day

Time frame
At 1 month, 2 months and 3 months
3

Impact of ketamine on headache duration after infusion

Impact of ketamine on duration of headache at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, from the headache diary maintained by patient

Time frame
At 1 month, 2 months and 3 months
4

Impact on sleep efficiency after ketamine infusion

Impact of ketamine on efficiency of sleep at one month (4 weeks), two month (week 5-8) and three month (week 9-12) month after infusion, measured with an actigraphy device

Time frame
At 1 month, 2 months and 3 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University Health Network, Toronto

Lead sponsor

The Canadian Pain Society

Collaborator

Pfizer

Collaborator

Source ClinicalTrials.gov
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