Clinical trial NCT06957704: Evaluation of the Efficacy and Safety of Subcutaneous Ketamine in the Treatment of Depressive Episode With Suicidal Ideation and/or Behavior in Adolescents
Official title: Evaluation of the Efficacy and Safety of Subcutaneous Ketamine in the Treatment of Depressive Episode With Suicidal Ideation and/or Behavior in Adolescents
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Depressive Disorder
Suicidal Ideas
Keywords: Adolescent
Ketamine
Major Depressive Disorder
Midazolam
Lead sponsor: Federal University of São Paulo
Sponsor class: OTHER
First posted: 2025-05-04
Enrollment: 60
Sex: ALL
Minimum age (years): 12
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Evaluate the efficacy and safety of subcutaneous ketamine added to usual treatment in the management of depressive episodes with suicidal ideation or behavior in adolescent patients, compared to usual treatment added to placebo (midazolam).

Detailed description: Depression affects approximately 8% of adolescents, with an estimated 60% showing inadequate response to current standard treatments. Ketamine, a glutamatergic modulator, has demonstrated efficacy in adults with treatment-resistant depression and has shown promising preliminary results in adolescent populations. This Phase III, randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy and safety of subcutaneous ketamine as an adjunctive treatment for adolescents experiencing a major depressive episode with active suicidal ideation and/or behavior.

Participants will be randomized into two parallel groups to receive either subcutaneous ketamine (0.5 to 1 mg/kg) or an active placebo (1 mg midazolam diluted in 5 ml of 0.9% saline), administered twice weekly for four weeks. All participants will continue their usual treatment regimens. A two-week post-treatment follow-up period will be conducted to assess the persistence of effects and monitor safety outcomes.

Clinical assessments include diagnostic and symptom severity scales validated for pediatric populations. The efficacy will be primarily measured by depression remission and response, while safety will be assessed via adverse event monitoring and clinical examination. The trial will include 30 participants per group, providing 80% power to detect a clinically significant difference of 8.7 points on the Montgomery-Åsberg Depression Rating Scale (MADRS) between groups.

Eligibility criteria: Inclusion Criteria:

* Age between 12 and 19 years.
* Diagnosis of Major Depressive Episode, unipolar, made through the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS-PL) administered by experienced evaluators, using DSM-5 criteria.
* Under usual treatment for Major Depressive Episode, including clinically indicated psychopharmacological treatment and/or psychosocial treatment at one of the two collaborating clinics (DICA and Conversas de Vida / Unifesp).
* Score ≥ 25 on the MADRS (Montgomery-Åsberg Depression Rating Scale).
* Score ≥ 28 on the CDRS (Children Depression Rating Scale).
* Score ≥ 2 on the Columbia Suicide Severity Rating Scale (C-SSRS).
* History of suicide attempt or significant suicidal ideation or planning with a plan or intention requiring emergency evaluation in the last 30 days.

Exclusion Criteria:

* Presence of the following psychiatric comorbidities: Autism Spectrum Disorder, Bipolar Disorder, Schizophrenia, Schizoaffective Disorder, or psychiatric disorder secondary to physical illness, and history of ketamine or other substance abuse or dependence in the last 6 months.
* Presence of Intellectual Disability (assessed by IQ testing).
* Presence of the following clinical comorbidities: history of myocardial infarction, congenital heart disease, decompensated cardiac arrhythmia, decompensated hypertension, porphyria, stroke, brain trauma with loss of consciousness, intracranial hypertension, hydrocephalus, central nervous system tumors, or central nervous system abnormalities.
* Previous treatment for depression with esketamine.
* Allergy to esketamine.
* If female: pregnancy or breastfeeding.

Primary outcomes:
measure: Change From Baseline in Montgomery-Asberg Rating Scale (MADRS) Total Score at 24 Hours Post First Dose
timeFrame: Baseline (predose) and 24 hours post first dose
Secondary outcomes:
measure: Remission and Response of Suicidal Ideation and Behavior Assessed by the Columbia-Suicide Severity Rating Scale (C-SSRS)
timeFrame: Baseline (predose) and 24 hours post first dose
Other outcomes:
Locations:
Study officials:
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