Clinical TrialTreatment-Resistant Depression (TRD)KetamineCompleted

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

Open-label, single-group biomarker pilot (n=9) testing intranasal ketamine (40 mg, mucosal atomization) in treatment-resistant depression with MRI and blood assays before and after treatment.

Target Enrollment
9 participants
Study Type
Phase II/III interventional
Design
Non-randomized

Detailed Description

Single-group, open-label pilot enrolling nine participants with treatment-resistant major depressive disorder to identify predictors of response to intranasal ketamine using MRI and blood biomarkers.

Participants undergo blood sampling and magnetic resonance imaging before and after intranasal ketamine administration (40 mg via mucosal atomization) and receive a subsequent second intranasal treatment; outcomes focus on biomarker change associated with clinical response.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Study Arms & Interventions

Open label

experimental

Open label intranasal ketamine

Interventions

  • Ketamine40 mg
    via Other• two sessions• 2 doses total

    Intranasal administration via mucosal atomization device; two intranasal treatments (baseline and subsequent).

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Male or female, 18 to 65 years of age, inclusive, at screening.
  • 2. 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.
  • 3. 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).
  • 4. Diagnosed with Major Depressive Disorder (MDD), single or recurrent, and currently experiencing a major depressive episode of at least eight weeks in duration, prior to screening, according to DSM-5; diagnosis made by site psychiatrist and supported by SCID-5.
  • 5. History of treatment-resistant depression (TRD) as assessed by MGH ATRQ; defined as failure to achieve a satisfactory response to at least 1 antidepressant course of ≥8 weeks.
  • 6. Depression of at least moderate severity (CGI-S ≥4).
  • 7. In good general health as ascertained by medical history, physical examination, clinical laboratory evaluations, and ECG.
  • 8. If female, non-childbearing potential or use of acceptable form of birth control; negative urinary pregnancy test at screening and baseline; willing and able to continuously use contraception during study.
  • 9. Body mass index between 18-35 kg/m2.
  • 10. Concurrent benzodiazepine therapy allowed if ≤2 mg lorazepam (or equivalent) per day and stable for past 4 weeks.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Female of childbearing potential unwilling to use one of the specified forms of birth control during the study.
  • 2. Pregnant or breastfeeding, or positive pregnancy test at screening or baseline.
  • 3. Current diagnosis of a substance use disorder, except nicotine dependence, at screening or within 6 months prior to screening.
  • 4. History of bipolar disorder, schizophrenia or schizoaffective disorder, or any history of psychotic symptoms in current or previous depressive episodes.
  • 5. History of anorexia nervosa, bulimia nervosa, or eating disorder not otherwise specified within 5 years of screening.
  • 6. In the judgment of the investigator, subject considered at significant risk for suicidal behaviour during participation.
  • 7. Dementia, delirium, amnestic, or other cognitive disorder.
  • 8. Clinically significant abnormality on screening physical exam that might affect safety, participation, or confound results.
  • 9. Current episode of: hypertension (systolic ≥160 mmHg or diastolic ≥100 mmHg at screening or within 1.5 hours prior to ketamine on two of three measurements); recent myocardial infarction (within 1 year); syncopal event within past year; congestive heart failure (NYHA >2); angina pectoris; heart rate <45 or >110 bpm at screening or Visit 3; QTcF ≥450 ms at screening or Visit 3.
  • 10. Chronic lung disease excluding asthma.
  • 11. Lifetime history of brain surgery, encephalitis, meningitis, degenerative CNS disorder, epilepsy, intellectual disability, or significant head trauma within past 2 years.
  • 12. Screening laboratory abnormalities or requiring exclusionary concomitant medications per protocol (see protocol Appendix/Table 1 for specific hematology and chemistry thresholds).
  • 13. History of hypothyroidism on stable replacement for <2 months prior to screening.
  • 14. History of hyperthyroidism treated <6 months prior to screening.
  • 15. Positive screening urine test for drugs of abuse (cannabinoids, cocaine, amphetamines, barbiturates, opiates) unless allowed per protocol and with agreement to abstain.
  • 16. History of narrow angle glaucoma.
  • 17. LFTs meeting exclusion criteria or history of hepatic or renal dysfunction.
  • 18. Self-reported history of ketamine or hallucinogen abuse or misuse.

Study Details

Locations

Nathan Kline Institute — Orangeburg, New York, United States

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