Oral and Sublingual Ketamine

NCT07683988 | Not Yet Recruiting Phase 1

• 1 other identifier: 127065
• Study Type: interventional
• Target: 10
• Locations: 0 countries
• Sites: N/A

Brief Summary

Major Depressive Disorder (MDD) is one of the most common and severe mental illnesses in the world. Ketamine treatment, especially intravenous ketamine (IVK) and intranasal esketamine (INE), is becoming more popular and is being used more. But these ways of administering aren't perfect. They mostly have problems with cost, accessibility, and the issues of administering. The oral and sublingual routes of ketamine are cheaper alternatives, but they haven't been looked into as much in the medical and academic circles. This is a small pilot feasibility study, involving ten patient participants who will be randomly assigned to take ketamine by oral and sublingual routes as part of a single-blind, crossover design. A local London pharmacy-Ultimate Care Compounding will provide the ketamine formulations. Ten patients between 18 and 65 years old with Major Depressive Disorder will be recruited from the Mental Health Care Programs at LHSC, Victoria Hospital and SJHC, Parkwood Institute, (that has treatment resistant depression treatment focus). After a screening baseline visit, which will include clinical interviews with medication reconciliation, psychiatric evaluations, routine standard laboratory tests, and an electrocardiogram (ECG). Due to capacity limitations at the Centre for Clinical Investigation and Therapeutics (CCIT), a maximum of 5 participants will undergo pharmacokinetic sampling simultaneously, enrolment will proceed in two sequential groups with treatment order assigned by group. Group A (n=5): The first 5 eligible participants will receive oral ketamine in Treatment Period 1 and sublingual ketamine in Treatment Period 2. Group B (n=5): The next 5 eligible participants will receive sublingual ketamine in Treatment Period 1 and oral ketamine in Treatment Period 2. Recruitment for Group B will commence once Group A has completed the clinical intervention phase. During Monday and Thursday of each of Weeks 1 and 2, Group A will receive oral ketamine, while Group B will receive sublingual ketamine. Weeks 3 and 4 are a washout period. In Weeks 5 and 6, on Mondays and Thursdays, groups will switch to the other form of administration \[See flowchart of study procedure\]. Weeks 7 and 8 are washout periods to ensure consistency with the first half of the study and provide a similar framework for clinical assessments. Blood samples will be collected at 2 time points at the Center for Clinical Investigation and Therapeutics at University Hospital. The study goal is to help define safe and effective oral/SL ketamine doses based on Pharmacokinetic profiles.

Conditions

Major Depression Severe

Keywords

ketamine; Depression

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic measures

  Plasma concentration of ketamine Plasma concentration of norketmaine Area Under Curve from 0 to 8 hours Area Under Curve from 8 hours to infinity Half-life of the log-linear phase Cmax (i.e. peak plasma drug concentration) Tmax (i.e. the time taken to reach the maximum concentration).

  Plasma samples will be collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, and 8 hours of the first day of weeks 1 and 5.

Secondary Outcomes (2)

• Montgomery-Aspberg Depression Rating Scale (MADRS).

  This scale will be used at screening and then: Week 1 and Week 2 - biweekly Week 3 and 4 - once a week Week 5 and 6 - biweekly Week 7 and 8 - once a week

• Hamilton Depression Rating Scale (HAM-D17)

  This scale will be used at screening and then: Week 1 and Week 2 - biweekly Week 3 and 4 - once a week Week 5 and 6 - biweekly Week 7 and 8 - once a week

Study Arms (2)

First part of the study

EXPERIMENTAL

Five patients will receive 75 mg of oral ketamine in weeks 1-2, weeks 3-4 are washout and weeks 5-6 they will crossover to receive 75 mg of sublingual keatmaine.

Drug: 75 mg of oral ketamine; Drug: Sublingual ketamine 75 mg

Second part of the study

EXPERIMENTAL

Five patients will receive 75 mg of sublingual ketamine in weeks 1-2, weeks 3-4 are washout and weeks 5-6 they will crossover to receive 75 mg of oral keatmaine.

Drug: 75 mg of oral ketamine; Drug: Sublingual ketamine 75 mg

Interventions

75 mg of oral ketamine DRUG

Ketamine in the oral preperation or form

First part of the study; Second part of the study

Sublingual ketamine 75 mg DRUG

Sublingual preparation of ketamine

First part of the study; Second part of the study

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Age: Between 18 and 65 years (inclusive) at the time of screening.
• Weight: Equal to or greater than 50 kg (110 lbs).
• Diagnosis: A current diagnosis of Major Depressive Disorder (MDD), moderate to severe in intensity, as defined by the DSM-5 criteria.
• Current Episode: Experiencing a moderate to severe Major Depressive Episode (MDE) at screening.
• Ongoing Treatment: Actively receiving pharmacological treatment for MDD at the time of enrollment.
• Treatment Resistance: Documented history of inadequate response to at least two antidepressant medications, each from a different pharmacological class, administered at an adequate dose and duration.
• Capacity and Consent: Able and willing to provide written informed consent after understanding the nature, risks, and potential benefits of the study.
• Clinical Oversight: Currently under the regular care of a psychiatrist or general practitioner (GP).
• Support System: Has a responsible adult (e.g., family member or caregiver) who can accompany them from study visits or ensure safe transportation after ketamine has been used.
• Able to speak, read and understand English
• Participants will be excluded if any of the following criteria apply:
• Suicidality: Active suicidal ideation with plan or intent, or suicidal behavior, within the past 3 months.
• Concomitant Medications: Use of medications that may pose a risk of respiratory depression or serious adverse events when combined with ketamine (e.g., benzodiazepines, opioids, barbiturates).
• Medical Comorbidities: Presence or history of significant or unstable medical conditions that could interfere with study participation or pose a safety risk, including but not limited to cerebrovascular accident, cardiac decompensation, large vessel aneurysms, glaucoma etc.. Participants with clinically significant laboratory abnormalities, as determined by the investigator, will also be excluded.
• Hypersensitvity to ketamine

Sponsors & Collaborators

• Western University, Canada: lead

MeSH Terms

Conditions

Depression

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Central Study Contacts

Rohit Lodhi, MD

CONTACT

+1-519-646-6100; rlodhi2@uwo.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor (Dept of Psychiatry, Schulich School of Medicine and Dentistry)

Model Details: This pilot study will characterise the pharmacokinetic profiles of oral and sublingual ketamine (75 mg) in patients with MDD using a crossover design in which each participant serves as their own control. 10 patients will be recruited and the study will be done in two phases/parts that will be 5 participants each.

Study Record Dates

• First Submitted: May 23, 2026
• First Posted: July 6, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: July 6, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share