Low-dose Ketamine Infusion Among Adolescents With Treatment-resistant Depression

NCT05045378 | Completed Phase 4

• 1 other identifier: 2020-02-015A
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

In the past decades, the prevalence of adolescent depression and suicide increased significantly in Taiwan and worldwide. To date, the suicide mortality is the second mortality cause in the adolescent and young adult population in Taiwan. Previous studies reported that up to 40% of adolescents with major depressive disorder did not respond to at least two traditional antidepressants with the optimal dose and adequate duration. Those patients would be considered the cases with treatment-resistant depression (TRD), which is related to the poor prognosis, chronic depressive course, higher suicidal risk, severer cognitive dysfunction, and greater family burdens. However, much less studies investigated the treatment strategy for adolescent TRD compared with that for adult TRD. In this decade, low-dose ketamine infusion has been proved as a rapid-acting antidepressant for adult patients with TRD. In recent 5 years, the investigators study team finished two randomized, double-blind, and placebo-control trials to support the rapid antidepressant and anti-suicidal effect in Taiwanese adult patients with TRD. The investigators published several SCI studies about the investigators clinical findings and the underlying brain mechanisms. In the following 4 years, the investigators will conduct a new randomized, double-blind, and placebo-control trial in the adolescent TRD. It will be the first clinical trial for ketamine effect in adolescent TRD worldwide. The investigators will enroll 54 adolescents aged between 13 and 29 with TRD in four years. The investigators hypothesize that low-dose ketamine will be effective and well tolerable for adolescents with TRD.

Conditions

Treatment-resistant Depression; Major Depressive Disorder

Keywords

adolescent; ketamine; N-methyl-D-aspartate receptor (NMDAR) antagonist

Outcome Measures

Primary Outcomes (3)

• Changes in depressive symptoms measured by Montgomery-Åsberg Depression Rating Scale (MADRS) in adolescents with treatment-resistant depression.

  Higher MADRS score indicates more severe depression. The overall score ranges from 0 to 60.

  clinical visit or telephone visit evaluation times are Day 1, 2, 3, 4, 5, 6, 7, 14, and 28

• Changes in depressive symptoms measured by Hamilton Rating Scale for Depression (HAMD) in adolescents with treatment-resistant depression.

  Higher HAMD score indicates more severe depression. The overall score ranges from 0 to 52.

  clinical visit or telephone visit evaluation times are Day 1, 2, 3, 4, 5, 6, 7, 14, and 28

• Changes in depressive symptoms measured by Children's Depression Rating Scale-Revised (CDRS-R) in adolescents with treatment-resistant depression.

  Higher CDRS-R score indicates more severe depression. The overall score ranges from 17 to 113.

  clinical visit or telephone visit evaluation times are Day 1, 2, 3, 4, 5, 6, 7, 14, and 28

Study Arms (3)

1. Two 0.045mg/kg midazolam infusions

ACTIVE COMPARATOR

Two 0.045mg/kg midazolam infusions as active placebo

Drug: Midazolam (active placebo)

2. First 0.045mg/kg midazolam infusion and Second 0.5mg/kg ketamine infusion

EXPERIMENTAL

Single ketamine infusion + Single midazolam placebo infusion

Drug: Ketamine and Midazolam (active placebo)

3. Two 0.5mg/kg ketamine infusions

EXPERIMENTAL

Repeated (Two) ketamine infusions: Two 0.5mg/kg ketamine infusions

Drug: Ketamine

Interventions

Midazolam (active placebo) DRUG

Arm1: Two 0.045mg/kg midazolam infusions at Day1 and Day3。

1. Two 0.045mg/kg midazolam infusions

Ketamine and Midazolam (active placebo) DRUG

Arm2: First 0.045mg/kg midazolam infusion and Second 0.5mg/kg ketamine infusion。

2. First 0.045mg/kg midazolam infusion and Second 0.5mg/kg ketamine infusion

Ketamine DRUG

Arm3: Two 0.5mg/kg ketamine infusions。

3. Two 0.5mg/kg ketamine infusions

Eligibility Criteria

• Age: 13 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Major depressive episode including unipolar and bipolar depression, according to DSM- 5 criteria and MINI-adolescent version (Mini-International Neuropsychiatric Interview; MINI) diagnostic interview.
• Age 13 to 19 years old.
• Body weigh ≧ 30 kg.
• Treatment-resistant depression, which is defined as poor or unsatisfactory response to at least two different antidepressants administered at an adequate dosage and for an adequate treatment duration
• Still prominent depressive symptoms with at least 4-week treatment of medication treatment or psychotherapy
• Voluntary patients and their parents or guardians with signed informed consent proved by institutional review board (IRB)

You may not qualify if:

• Major medical conditions (e.g., head injury, epilepsy, severe renal diseases and cancer).
• Other axis I psychiatric disorders such as schizophrenia, delusional disorder, organic brain syndrome, and dementia.
• Pregnancy.
• Substance abuse in previous 6 months such as cocaine, marijuana, opium, ketamine, PCP (phencyclidine)。
• Current use of NMDA receptor antagonist (Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan)
• Alcohol abuse / dependence within 6 months.
• Attempt suicide in hospital.
• Allergy to ketamine
• Abnormal liver function in recent 3 months。
• Abnormal ECG (i.e.:arrhythmia)。
• Fever or infection in recent 5 days。

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

Study Sites (1)

Taipei Veterans General Hospital, Taiwan

Taipei, 112, Taiwan

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Interventions

Midazolam; Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Mu-Hong Chen, M.D., Ph.D.

  Taipei Veterans General Hospital, Taiwan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2021
• First Posted: September 16, 2021
• Study Start: March 15, 2022
• Primary Completion: November 30, 2024
• Study Completion: November 30, 2024
• Last Updated: September 5, 2025

Record last verified: 2022-04

Locations

TW (1)