Ketamine as an Adjunctive Therapy for Major Depression

NCT03256162 | Completed Phase 1 Results DMC

• 2 other identifiers: 01/172016-004764-18
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.

Conditions

Major Depressive Episode; Unipolar Depression; Bipolar Depression

Keywords

ketamine; glutamate

Outcome Measures

Primary Outcomes (1)

• The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)

  The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms. Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later. Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.

  15 weeks

Secondary Outcomes (6)

• The Quick Inventory of Depressive Symptoms, Self-report Version (QIDS-SR16)

  15 weeks

• The Clinician-Administered Dissociative States Scale (CADSS)

  4 weeks

• The Brief Psychiatric Rating Scale (BPRS)

  4 weeks

• Young Mania Rating Scale (YMRS; Mood Item)

  4 weeks

• The Patient-Rated Inventory of Side Effects (PRISE)

  4 weeks

Study Arms (2)

Ketamine

EXPERIMENTAL

Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.

Drug: Ketamine

Midazolam

ACTIVE COMPARATOR

Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.

Drug: Midazolam

Interventions

Ketamine DRUG

A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.

Also known as: Ketalar

Ketamine

Midazolam DRUG

A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.

Also known as: Hypnovel

Midazolam

Eligibility Criteria

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

You may qualify if:

• ≥18 years old
• Hamilton Rating Scale for Depression-24 item version (HRSD-24) score of ≥21
• Voluntary admission for treatment of an acute depressive episode
• Meet Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-V) criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)

You may not qualify if:

• Current involuntary admission
• Medical condition rendering unfit for ketamine/midazolam
• Active suicidal intention
• Dementia
• History of Axis 1 diagnosis other than major depression
• Electroconvulsive Therapy (ECT) administered within the last two months
• Alcohol/substance dependence in previous six-months
• Pregnancy or inability to confirm use of adequate contraception during the trial
• Breastfeeding women

Sponsors & Collaborators

• St Patrick's Hospital, Ireland: lead

Study Sites (1)

St Patrick's University Hospital

Dublin, D8, Ireland

Location

Related Publications (1)

• Gallagher B, Foley M, Slattery CM, Gusciute G, Shanahan E, McLoughlin DM. Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial). HRB Open Res. 2022 Jan 27;3:90. doi: 10.12688/hrbopenres.13182.2. eCollection 2020.

  PMID: 35036831 DERIVED

MeSH Terms

Conditions

Depressive Disorder; Bipolar Disorder

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

As this is a pilot trial, participant numbers are low.

Results Point of Contact

• Title: Dr Bronagh Gallagher
• Organization: Trinity College Dublin

bgallag@tcd.ie

01 249

Study Officials

• Declan M McLoughlin, PhD

  St Patrick's Mental Health Services and Trinity College Dublin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 21, 2017
• Study Start: September 7, 2017
• Primary Completion: September 21, 2018
• Study Completion: September 21, 2018
• Last Updated: January 18, 2020
• Results First Posted: January 18, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

IE (1)