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Depressive Disorder, Treatment-ResistantPhase 2/3NCT04216888

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

A Phase 2/3 study testing Ketamine Hydrochloride in people with Depressive Disorder, Treatment-Resistant, run by Dan Iosifescu at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Depressive Disorder, Treatment-Resistant
What is being tested?
Ketamine Hydrochloride
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
26 Jun 2019to 28 Dec 2020
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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:
  • 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.
  • Negative urinary pregnancy test at screening, confirmed by a negative urinary pregnancy test at baseline, prior to receiving ketamine treatment.
  • 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.

Who cannot join

  • 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.
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  • 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.
  • Heart rate <45 or >110 beats per minute at screening or Visit 3 ( first ketamine administration).
  • QTcF (Fridericia-corrected) ≥450 msec at screening or Visit 3 (first ketamine administration).
  • Chronic lung disease excluding asthma.
  • Lifetime history of surgical procedures involving the brain or meninges, encephalitis, meningitis, degenerative central nervous system (CNS) disorder (e.g., Alzheimer's or Parkinson's Disease), epilepsy, mental retardation, or any other disease/procedure/accident/intervention which, according to the screening clinician, is deemed associated with significant injury to or malfunction of the CNS, or history of significant head trauma within the past 2 years.
  • Presents with any of the following lab abnormalities:
  • Thyroid stimulating hormone (TSH) outside of the normal limits and clinically significant as determined by the investigator. Free thyroxine (T4) levels may be measured if TSH level is high. Subject will be excluded if T4 level is clinically significant.
  • Patients with diabetes mellitus fulfilling any of the following criteria:
  • Unstable diabetes mellitus defined as glycosylated hemoglobin (HbA1c) >8.5% at screening.
  • Admitted to hospital for treatment of diabetes mellitus or diabetes mellitus-related illness in the past 12 weeks.
  • Not under physician care for diabetes mellitus. iv. Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to screening. For thiazolidinediones (glitazones) this period should not be less than 8 weeks.
  • Any other abnormal laboratory result(s), clinically significant in the opinion of the investigator, at the time of the screening.
  • History of hypothyroidism and has been on a stable dosage of thyroid replacement medication for less than 2 months prior to screening. (Subjects on a stable dosage of thyroid replacement medication for at least 2 months or more prior to screening are eligible for enrollment.)
  • History of hyperthyroidism which was treated (medically or surgically) less than 6 months prior to screening.
  • History of positive screening urine test for drugs of abuse at screening: cannabinoids (if the patient has a legitimate medical prescription for cannabis, patient must agree to abstain during the entirety of the study and to have a negative test at baseline), cocaine, amphetamines, barbiturates, opiates (unless use is in accordance with guidance provided in Appendix 1, table of allowed and excluded medications).
  • Patients with exclusionary laboratory values (see Table 1) or requiring treatment with exclusionary concomitant medications (see Appendix 1).
  • Patients with a history of narrow angle glaucoma.
  • Liver or renal Function Tests (LFTs) which meet the exclusion criteria in Table 1, or a history of hepatic or renal dysfunction.
  • Self-reported history of a ketamine or hallucinogen abuse or misuse.
  • TABLE 1: EXCLUSIONARY SAFETY VALUES OF POTENTIAL CLINICAL CONCERN Hematology Leukocytes <2 or >17.5 x 103/mm3 Platelets <75 or >700 x 103/mm3 Chemistry Total bilirubin >2 times the upper limit of the reference range AST >2.5 times upper limit of the reference range ALT >2.5 times upper limit of the reference range GGT >2.5 times upper limit of the reference range Alk Phosphatase >2.5 times upper limit of the reference range Creatinine >1.3 times upper limit of the reference range BUN/Urea >1.3 times upper limit of the reference range Glucose < 70 mg/dl or >2 times the limits of the reference range Uric acid >1.5 times upper limit of the reference range
  • LFTs higher than 2.5 times ULN will be exclusionary.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Nathan Kline Institute

    Orangeburg, New York, 10962

Other trials in United States

About this study

Official title: Biomarkers of Response to Ketamine in Depression

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.

Being tested
Ketamine Hydrochloride
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Ketamine HydrochlorideDrug

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

Study groups in NCT04216888
Study groupRoleWhat they receive
Open labelExperimentalOpen label intranasal ketamine
Receives: Drug: Ketamine Hydrochloride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 24 hours

  2. Cortical thickness

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

    Measured: within 48 hours (pretreatment)

Secondary outcomes (2)

  1. Neural response to affective stimuli

    We will test for baseline differences in functional anisotropy of white matter tracts which differentiate responders and non-responders to ketamine.

    Measured: within 48 hours (post treatment)

  2. Neural response to affective stimuli

    We will test for changes in cognitive control network (CCN) activation and functional connectivity (FC) of anterior aspects of the CCN (middle frontal gyrus [MFG] and dorsal anterior cingulate cortex [dACC]) during an emotional regulation task.

    Measured: within 48 hours (pretreatment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jan 2020
  2. Study start26 Jun 2019
  3. Primary completion28 Dec 2020
  4. Study completion28 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04216888
Sponsor's protocol ID
KetBiomarkers
Status last verified
Jan 2021
First submitted
26 Aug 2019
Last updated
22 Jan 2021
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Ketamine Hydrochloride in people with Depressive Disorder, Treatment-Resistant, run by Dan Iosifescu at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 35 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Montgomery and Asberg Depression Rating Scale (MADRS) (time frame: 24 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04216888.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.

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