Biomarkers of Response to Ketamine in Depression: MRI and Blood Assays Before and After Open Label Intranasal Ketamine

NCT04216888 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: KetBiomarkers
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot study aims to identify predictors of response to intranasal ketamine treatment in patients with treatment-resistant depression. Participants will give a sample of blood and undergo magnetic resonance imaging before and after a single intranasal ketamine treatment. Participants will subsequently receive a second intranasal ketamine treatment.

Conditions

Depressive Disorder, Treatment-Resistant

Outcome Measures

Primary Outcomes (2)

• Change in Montgomery and Asberg Depression Rating Scale (MADRS)

  Montgomery and Asberg Depression Rating Scale (MADRS), with scores ranging from 0-60; higher scores indicate more severe depression. Change will be calculated as the difference between MADRS scores at baseline (day of but prior to first ketamine treatment) and a 24 hour follow-up visit.

  24 hours

• Cortical thickness

  We will test for baseline differences in cortical thickness which differentiate responders and non-responders to ketamine.

  within 48 hours (pretreatment)

Secondary Outcomes (2)

• Neural response to affective stimuli

  within 48 hours (post treatment)

• Neural response to affective stimuli

  within 48 hours (pretreatment)

Study Arms (1)

Open label

EXPERIMENTAL

Open label intranasal ketamine

Drug: Ketamine Hydrochloride

Interventions

Ketamine Hydrochloride DRUG

Intranasal administration of 40mg ketamine hydrochloride using an intranasal mucosal atomization device

Open label

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, 18 to 65 years of age, inclusive, at screening.
• Able to read, understand, and provide written, dated informed consent prior to screening. Participants will be deemed likely to comply with study protocol and communicate with study personnel about adverse events and other clinically important information.
• Ability to participate in MRI (no history of claustrophobia, no presence of metallic foreign bodies incompatible with MRI, as assessed with MRI checklist and clinical interview).
• Diagnosed with Major Depressive Disorders (MDD), single or recurrent, and currently experiencing a major depressive episode (MDE) of at least eight weeks in duration, prior to screening, according to the criteria defined in the Diagnosis and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis of MDD will be made by a site psychiatrist and supported by the Structured Clinical Interview for DSM-5 (SCID-5).
• Has a history of treatment-resistant depression (TRD), as assessed by the investigator using the Mass General Hospital Antidepressant Treatment History Questionnaire (MGH ATRQ). TRD is defined as failure to achieve a satisfactory response (e.g., less than 50% improvement of depression symptoms), as perceived by the participant, to at least 1 "treatment course" of a therapeutic dose of an antidepressant therapy of at least 8 weeks duration (including the current antidepressant treatment). The adequacy of dose and duration of the antidepressant therapy will be determined as per the MGH ATRQ criteria.
• Depression is of at least "moderate" severity, as determined by a Clinical Global Impression-Severity scale (CGI-S) score greater than or equal to 4).
• In good general health, as ascertained by medical history, physical examination (including measurement of vital signs), clinical laboratory evaluations, and electrocardiogram (ECG).
• If female, a status of non-childbearing potential or use of an acceptable form of birth control per the following specific criteria:
• a. Non-childbearing potential (e.g., physiologically incapable of becoming pregnant, i.e., permanently sterilized (status post hysterectomy, bilateral tubal ligation), or is post-menopausal with her last menses at least one year prior to screening); or b. Childbearing potential, and meets the following criteria: i. Childbearing potential, including women using any form of hormonal birth control, on hormone replacement therapy started prior to 12 months of amenorrhea, using an intrauterine device (IUD), having a monogamous relationship with a partner who has had a vasectomy, or is sexually abstinent.
• ii. Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at baseline, prior to receiving ketamine treatment.
• iii. Willing and able to continuously use one of the following methods of birth control during the course of the study, defined as those which result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly: implants, injectable or patch hormonal contraception, oral contraceptives, IUD, double-barrier contraception, sexual abstinence. The form of birth control will be documented at screening and baseline.
• Body mass index between 18-35 kg/m2.
• Concurrent benzodiazepine therapy will be allowed if the dose is less than or equal to 2mg of lorazepam (or the equivalent) per day and stable for the past 4 weeks.

You may not qualify if:

• Female of childbearing potential who is not willing to use one of the specified forms of birth control during the study.
• Female that is pregnant or breastfeeding.
• Female with a positive pregnancy test at screening or baseline.
• Current diagnosis of a substance use disorder, except for nicotine dependence, at screening or within 6 months prior to screening.
• History of bipolar disorder, schizophrenia or schizoaffective disorders, or any history of psychotic symptoms in the current or previous depressive episodes.
• History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified, within 5 years of screening.
• In the judgment of the investigator, the subject is considered at significant risk for suicidal behavior during his/her participation in the study.
• Has dementia, delirium, amnestic, or any other cognitive disorder.
• Has a clinically significant abnormality on the screening physical examination that might affect safety, study participation, or confound interpretation of study results according to the study clinician.
• Current episode of:
• Hypertension, Stage 1 as defined by a systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg at screening (Visit 1) or within 1.5 hours prior to ketamine administration on two of three measurements (standing and supine) at least 15 minutes apart.
• Recent myocardial infarction (within one year) or a history of myocardial infarction.
• Syncopal event within the past year.
• Congestive heart failure (CHF): New York Heart Association Criteria \>Stage 2
• Angina pectoris.

Sponsors & Collaborators

• Dan Iosifescu: lead

Study Sites (1)

Nathan Kline Institute

Orangeburg, New York, 10962, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Dan Iosifescu, MD, MSc

  Nathan Kline Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director of Clinical Reserach

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: January 3, 2020
• Study Start: June 26, 2019
• Primary Completion: December 28, 2020
• Study Completion: December 28, 2020
• Last Updated: January 22, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)