Ketamine for Treatment Resistant Late-Life Depression

NCT02556606 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: CLNA-001-14F
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to examine the effectiveness of a single infusion of ketamine (KET), to determine which dose is optimal 7 days after infusion using Bayesian Adaptive Randomization, and to learn about how ketamine works in the body and brain in persons with late-life treatment resistant depression.

Conditions

Treatment Resistant Depressive Disorder

Keywords

ketamine; depression; treatment resistant; treatment resistant depression; late life depression; depression in the elderly; geriatric depression

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants Demonstrating at Least a 50% Reduction on Montgomery-Asberg Depression Rating Scale Scores

  To determine the best performing intervention among three sub-anesthetic doses of a single ketamine (0.1 mg/kg, 0.25 mg/kg, and 0.50 mg/kg) and midazolam (0.03 mg/kg) in Veterans with LL-TRD as measured by the percentage of participants demonstrating at least a 50% reduction from pre-treatment baseline on Montgomery-Asberg Depression Rating Scale (MADRS; score range 0 - 60, higher scores meaning more severe depression) scores at 7 days post-infusion.

  Day 7 post-infusion

Secondary Outcomes (1)

• Percentage of Patients With Continuation From Day 7 to Day 28 Post-infusion of at Least a 50% Improvement in MADRS

  28 days post-infusion follow-up

Other Outcomes (4)

• Change in Clinician-Administered Dissociative States Scale (CADSS)

  Baseline to 40 minutes after start of infusion

• Change in Resting-state Quantitative Electroencephalography (EEG) Frontal Gamma Band Power (Log of Microvolt Squared)

  Baseline to 30 minutes after start of infusion

• Change in Systolic Blood Pressure (Millimeters of Mercury, mm Hg)

  Baseline to 30 minutes after start of infusion

Study Arms (4)

Ketamine 0.10 mg/kg

EXPERIMENTAL

randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg

Drug: Ketamine

Ketamine 0.25 mg/kg

EXPERIMENTAL

randomly assigned to a single 40 min infusion of either KET 0.25mg/Kg

Drug: Ketamine

Ketamine 0.50 mg/kg

EXPERIMENTAL

randomly assigned to a single 40 min infusion of either KET 0.50mg/Kg

Drug: Ketamine

Midazolam 0.03 mg/kg

ACTIVE COMPARATOR

randomly assigned to a single 40 min infusion of either MID 0.03mg/Kg

Drug: Midazolam

Interventions

Ketamine DRUG

randomly assigned to a single 40 min infusion of either KET 0.1mg/Kg

Ketamine 0.10 mg/kg

Midazolam DRUG

single 40 min infusion of MID 0.03mg/Kg

Midazolam 0.03 mg/kg

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 55 years of age,
• Participants must fulfill DSM 5 criteria for a Major Depressive Episode (Unipolar), based on a structured diagnostic interview, the DSM 5 M.I.N.I. 7.0
• Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration),
• Participants have not responded to two or more adequate trials of FDA-approved antidepressants, determined by Antidepressant Treatment Response Questionnaire (ATRQ) criteria.
• Participants must score 14 or greater on the Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR), and score 27 on the Montgomery Asberg Depression Rating Scale (MADRS),
• Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document.

You may not qualify if:

• Patients currently on fluoxetine,
• History of schizophrenia, schizoaffective disorder or any psychotic disorder, or bipolar disorder,
• Documented history of a psychotic disorder in a first-degree relative,
• Current diagnosis of obsessive-compulsive disorder (OCD) or eating disorder \[bulimia nervosa or anorexia nervosa\],
• Alcohol or substance use \[except nicotine\] within the preceding 6 months,
• Patients with any clinically significant personality disorder that would, in the investigator's judgment, preclude safe study participation,
• Patients judged to be at serious and imminent suicidal or homicidal risk,
• Serious, unstable medical illnesses including respiratory \[obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics\], cardiovascular \[including ischemic heart disease and uncontrolled hypertension\], and neurologic \[including history of severe head injury\],
• For study entry, patients must be reasonable medical candidates for ketamine or midazolam infusion, as determined by a board-certified physician co-investigator during study Screening,
• Clinically significant abnormal findings of laboratory parameters \[including urine toxicology screen for drugs of abuse\], physical examination, or ECG,
• Hypertension (systolic BP \>160 mm Hg or diastolic BP \>90 mm Hg),
• Patients with one or more 11 seizures without a clear and resolved etiology,
• Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to Screening,
• Past intolerance or hypersensitivity to ketamine, or history of recreational use of phencyclidine (PCP) or ketamine,
• Past intolerance or hypersensitivity to midazolam,

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Michael E. DeBakey VA Medical Center, Houston, TX

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Murphy N, Lijffijt M, Ramakrishnan N, Vo-Le B, Vo-Le B, Iqbal S, Iqbal T, O'Brien B, Smith MA, Swann AC, Mathew SJ. Does mismatch negativity have utility for NMDA receptor drug development in depression? Braz J Psychiatry. 2022 Jan-Feb;44(1):61-73. doi: 10.1590/1516-4446-2020-1685.

  PMID: 33825765 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Marijn Lijffijt, PhD
• Organization: Michael E. DeBakey VA Medical Center

marijn.lijffijt@bcm.edu

3618274395

Study Officials

• Sanjay Mathew, MD

  Michael E. DeBakey VA Medical Center, Houston, TX

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: We use a Bayesian, adaptive, randomized design initially allocating subjects to 2 arms in a 1:3 ratio: ARM 1: MID 0.03 mg/kg (active placebo); ARM 2: four conditions KET 0.1 mg/kg, KET 0.25 mg/kg, KET 0.5 mg/kg or MID 0.03 mg/kg. After 1:1:1:1 allocation of the first 20 subjects to ARM 2, Bayesian adaptive randomization may stop for superiority, change randomization ratios and/or prune arms for futility based on the probability of a day 7 treatment response. ARM 1 remains open for allocation to ensure a placebo group sufficiently large for comparison with best dose KET. For analyses, MID of ARM 1 and ARM 2 will be combined so that there are 4 conditions (or arms) for final statistical analyses. We expected to enroll a maximum 72 patients.

Study Record Dates

• First Submitted: June 25, 2015
• First Posted: September 22, 2015
• Study Start: October 1, 2015
• Primary Completion: March 31, 2020
• Study Completion: March 31, 2020
• Last Updated: January 11, 2022
• Results First Posted: August 9, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)