NCT03102736

Ketamine and Nitroprusside for Depression

Completed Phase 2 Results posted Last updated 2 July 2020

What this trial tests

Phase 2 trial testing Placebos in Depression in 40 participants. Completed in 12 June 2019.

Timeline

14 February 2017

Primary endpoint
12 June 2019

12 June 2019

Quick facts

Lead sponsor	Icahn School of Medicine at Mount Sinai
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	40
Start date	14 February 2017
Primary completion	12 June 2019
Estimated completion	12 June 2019
Sites	1 location across United States

Drugs / interventions tested

• Placebos — full drug profile →
• Ketamine (ketamine) — full drug profile →
• Nitroprusside (NITROPRUSSIDE) — full drug profile →

Conditions studied

• Depression — all drugs for Depression →

Sponsor

Icahn School of Medicine at Mount Sinai

Who can join

Adults 21 to 65, any sex, with Depression. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Montgomery-Asberg Depression Rating Scale Primary · 24 hours after start of infusion

This is a 10-item instrument used for the evaluation of depressive symptoms in adults and for the assessment of any changes to those symptoms. Each of the 10 items is rated on a scale of 0 to 6, with differing descriptors for each item. These individual item scores are added together to form a total score, which can range between 0 (normal) and 60 (severe depression).

Group	Value	95% CI
Placebo and Ketamine	13.4	± 11.9
Nitroprusside and Ketamine	14.2	± 10.2

Clinician-Administered Dissociative States Scale Secondary · 240 minutes after start of infusion

This is used to measure dissociative effects during the infusions. The scale includes 23 clinician administered items scored from 0 (not at all) to 4 (extremely). The CADSS measures impairment in body perception, environmental perception, time perception, memory impairment, and feelings of unreality. Full scale from 0-92, with lower score indicating better health outcomes.

Group	Value	95% CI
Placebo and Ketamine	11.5	± 9.9
Nitroprusside and Ketamine	8.4	± 4.1

Brief Psychiatric Rating Scale (BPRS) Secondary · +240 minutes (after start of Placebo/Nitroprusside infusion)

BPRS used to assess acute behavioral changes during the infusions. Four key BPRS items for the positive (+) symptoms of psychosis will be used: conceptual disorganization, hallucinatory behavior, suspiciousness, and unusual thought content. Three items representing the negative (-) symptoms of psychosis will also be used: blunted affect, emotional withdrawal, and motor retardation. Each item scored 1-7. Full scale from 7 - 49, with higher score indicating more symptoms.

Group	Value	95% CI
Placebo and Ketamine	7.5	± 1.13
Nitroprusside and Ketamine	7.2	± 0.66

Adverse events — posted to ClinicalTrials.gov

Time frame: 24 hours after infusion. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo and Ketamine

Serious: 0/7 (0%)

Deaths: 0/7

Nitroprusside and Ketamine

Serious: 0/9 (0%)

Deaths: 0/9

Other adverse events (11 terms — click to expand)

Reaction	System	Placebo and Ketamine	Nitroprusside and Ketamine
Headache	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Paresthesia	Nervous system disorders	—	—
Akathisia	Nervous system disorders	—	—
Muscle Aches	Musculoskeletal and connective tissue disorders	—	—
Urinary Tract Infection	Renal and urinary disorders	—	—
Anxiety	Psychiatric disorders	—	—
Suicidal Ideation	Psychiatric disorders	—	—
Worsening MDD	Psychiatric disorders	—	—
Hypertension	Cardiac disorders	—	—

Data from ClinicalTrials.gov NCT03102736 adverse events section.

Sponsor's own description

The purpose of this study is to test the effects of the medication ketamine and the medication called nitroprusside in patients with major depression. Ketamine has both good and bad effects. Some studies have shown that ketamine improves depression. However, studies have also shown that it causes strange and sometimes unpleasant sensations referred to "psychotic" or "dissociative" symptoms. An example of a psychotic symptom would be hearing or seeing something that in reality is not there. The study team would like to see if nitroprusside can prevent the reported bad effects of ketamine without blocking the reported good effects. This might make ketamine a better treatment for depression.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Blood miR-144-3p: a novel diagnostic and therapeutic tool for depression.
   van der Zee YY, Eijssen LMT, Mews P, Ramakrishnan A, et al · · 2022 · cited 43× · PMID 35902629 · DOI 10.1038/s41380-022-01712-6
2. Whole blood transcriptional signatures associated with rapid antidepressant response to ketamine in patients with treatment resistant depression.
   Cathomas F, Bevilacqua L, Ramakrishnan A, Kronman H, et al · · 2022 · cited 36× · PMID 35013133 · DOI 10.1038/s41398-021-01712-0
3. Role of nitric oxide signaling in the antidepressant mechanism of action of ketamine: A randomized controlled trial.
   Bevilacqua L, Charney A, Pierce CR, Richards SM, et al · · 2021 · cited 4× · PMID 33522376 · DOI 10.1177/0269881120985147