Preoperative Ketamine and Perioperative Depression

NCT04220125 | Withdrawn Phase 4 DMC FDA Drug

• 1 other identifier: STU00211219
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Depressive symptoms, in patients with a life history of major depressive disorder (MDD), are very common in the general population, and are especially so in elderly adults undergoing surgery.Symptoms of depression at the time of surgery is associated with risk for postoperative complications.Attenuating depressive symptoms in patients undergoing surgery is thus a plausible but not adequately tested strategy for improving patient postoperative outcomes. Conventional treatment of depression takes weeks and, therefore, is not always a realistic option, particularly when surgery is urgent. Importantly, there are currently no guidelines for diagnosing and managing MDD in surgical patients. Given its association with complications including perioperative cognitive disorders such as delirium, and over longer periods of time with dementing disorders, the feasibility and efficacy of quick-acting treatments for depressive symptoms in surgical patients are direly needed. This need is particularly acute given the rising number of elderly patients undergoing surgery who are prone to depression and surgical complications. Aim 1: To assess the feasibility of enrolling patients in a clinical trial where a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) or midazolam (0.045 mg/kg) is given 1 to 3 days before surgery in the preoperative clinic as a strategy to improve depressive symptoms during the perioperative period. Aim 2: To obtain estimates of the variability in improvements of depressive symptoms (increase from baseline in MADRS score ≥ 2)1 day after surgery for patients given a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) 1 to 3 days before surgery compared with midazolam 0.045 mg/kg. Aim 3: To assess for the safety and tolerability of administration of a sub-anesthetic dose of ketamine (0.5 mg/kg over 40 min) given 1 to 3 days before surgery in the preoperative clinic (as an outpatient) by assessment of dysphoric symptoms or other complications including the need for hospitalization. Hypothesis: Aim 1: Hypothesis: Patients with preoperative depressive symptoms can be identified before surgery and successfully enrolled in a clinical trial comparing a sub-anesthetic dose of ketamine versus midazolam for improving perioperative depressive symptoms. Aim 2: Hypothesis: Compared with midazolam, a sub-anesthetic dose of ketamine given preoperatively leads to an improvement in MADRS score ≥ 2 on day 1 after surgery. Aim 3: Hypothesis: Compared with midazolam, a sub-anesthetic dose of ketamine is not associated with dysphoria or other complications.

Conditions

Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptoms in the perioperative period.

  Ketamine administration changes depressive symptoms perioperatively. Measured using Depression will be measured with the Montgomery-Asberg Depression Scale (MADRS) scale. Scale ranges from 0 no depresson- 60 severe depression.

  3 Days before surgery to 30 days after the surgical procedure

Secondary Outcomes (2)

• Change in depressive symptoms 1 day after surgery

  24 hours after surgical procedure

• Safety analsysis of administration of a sub-anesthetic dose of ketamine: CADSS

  65 minutes after study drug has been infused.

Study Arms (2)

Ketamine Group

EXPERIMENTAL

Ketamine 0.5 mg/kg over 40 min via intravenous catheter.

Drug: Ketamine Group

MIdazolam Group

ACTIVE COMPARATOR

Midazolam 0.045 mg/kg administered via intravenous catheter.

Drug: Midazolam injection

Interventions

Ketamine Group DRUG

Ketamine intravenous administration 0.5 mg/kg over 40 minutes.

Also known as: Ketamine

Ketamine Group

Midazolam injection DRUG

Midazolam intravenous administration 0.045 mg/kg IV over 40 minutes.

Also known as: Midazolam

MIdazolam Group

Eligibility Criteria

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

You may qualify if:

• Male or female patients age ≥ 65 years
• Planned lumbar surgery for degenerative disc disease or spinal stenosis involving 2 or more levels
• A life history of MDD (DSM-5 criteria) and a MADRS score ≥20
• Mini-Mental State Examination (MMSE) score ≥ 15
• MMSE is between15-26
• Ability to understand English.

You may not qualify if:

• MMSE \< 15
• History of psychosis
• Poorly controlled hypertension
• Pre-existing aneurysmal vascular disorders
• Cocaine or other illicit drug use.

Sponsors & Collaborators

• Northwestern University: lead

MeSH Terms

Conditions

Depressive Disorder

Interventions

Ketamine; Midazolam

Condition Hierarchy (Ancestors)

Mood Disorders; Mental 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

Study Officials

• Charles Hogue, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair, Department of Anesthesiology

Study Record Dates

• First Submitted: January 3, 2020
• First Posted: January 7, 2020
• Study Start: September 1, 2022
• Primary Completion: February 2, 2023
• Study Completion: February 2, 2023
• Last Updated: February 6, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share