NCT04234776

Brief Summary

The treatment of resistant depression should be optimized aiming at complete remission of symptoms, a complex condition due to several factors. Approximately 1/3 of patients with depressive disorders do not even respond to available antidepressants. Consequently, new molecules with robust action, fast effects and sustained improvement are currently being researched worldwide. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has emerged as a promising alternative due to its involvement in neurogenesis, synaptogenesis and consequent rapid improvement of depressive and suicidal symptoms with traditional intravenous (IV) use in sub dose (0.5 mg / kg). The therapeutic response of IV use has been short and requires monitoring in a hospital setting. There are no studies evaluating response to long-term ketamine use. Recent research has focused on identifying other routes of ketamine use such as intranasal and intramuscular (IM). The use of ketamine IM, despite the fact that there are few studies and small samples, can demonstrate efficacy in acute treatment and maintenance of depression, as well as low profile of side effects, greater accessibility potential, reduced costs and risks, patient comfort and possible expansion of resistant depression treatment capabilities in different settings.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
88

participants targeted

Target at P50-P75 for phase_4

Timeline
Completed

Started Apr 2018

Typical duration for phase_4

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 3, 2018

Completed
1.5 years until next milestone

First Submitted

Initial submission to the registry

October 7, 2019

Completed
4 months until next milestone

First Posted

Study publicly available on registry

January 21, 2020

Completed
4 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 3, 2020

Completed
10 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 3, 2021

Completed
Last Updated

January 21, 2020

Status Verified

December 1, 2019

Enrollment Period

2.2 years

First QC Date

October 7, 2019

Last Update Submit

January 15, 2020

Conditions

Depressive Disorder

Keywords

KetamineTreatment Resistant Depression

Outcome Measures

Primary Outcomes (3)

  • Change in depressive symptoms

    Montomery-Ă…sberg Depression Rating Scale (\[0-60\] higher scores: worse outcome). No improvement: MADRS ≤ 25% Partial response: MADRS ≥ 25% and \< 50% Response: MADRS ≥ 50% Remission: MADRS ≤10

    3 times a week in once month (Phase II)

  • Change in depressive symptoms

    Montgomery-Ă…sberg Depression Rating Scale (\[0-60\] higher scores: worse outcome). Recovery: Maintenance ≥ 6-8 months Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria)

    Once a week in six months (Phase III)

  • Change in depressive symptoms

    Montgomery-Åsberg Depression Rating Scale (\[0-60\] higher scores: worse outcome). Relapse: Full return of symptoms once remission has occurred or worsening ≤ 75% with lower percentage of improvement (HAM-D inclusion criteria).

    Once a week in once month (Phase IV)

Secondary Outcomes (46)

  • Depression symptoms

    Through study completion, an average of 1 year.

  • Clinical impressions-S

    Through study completion, an average of 1 year.

  • Clinical impressions-I

    Through study completion, an average of 1 year.

  • Electrocardiographic monitoring

    3 times a week in once month (Fase II) and once a week in six months (Phase III)

  • Blood Pressure (BP [mmHg]).

    3 times a week in once month (Fase II) and once a week in six months (Phase III)

  • +41 more secondary outcomes

Study Arms (2)

Rapid-acting antidepressant

EXPERIMENTAL

Subjects eligible to participate in the study will receive IM ketamine and will use 2 placebo tablets as randomized.

Drug: KetamineDiagnostic Test: CognitionOther: Suicide riskOther: Depression thoughtsOther: Quality of life and disabilityOther: Clinical and epidemiological factorsDevice: Safety of ketamine IMOther: Tolerability of ketamine IM

Comparator

ACTIVE COMPARATOR

Subjects eligible to participate in the study will receive IM saline and will use escitalopram 15 mg and aripiprazole 5 mg as randomized

Drug: KetamineDiagnostic Test: CognitionOther: Suicide riskOther: Depression thoughtsOther: Quality of life and disabilityOther: Clinical and epidemiological factorsDevice: Safety of ketamine IMOther: Tolerability of ketamine IM

Interventions

KetamineDRUG

(0,75 mg/kg) saline solution (15 mg) Escitalopram (5 mg) Aripiprazole

Also known as: Active comparator (escitalopram plus aripiprazole), Placebo
ComparatorRapid-acting antidepressant
CognitionDIAGNOSTIC_TEST

Composite tools

ComparatorRapid-acting antidepressant
Suicide riskOTHER

MADRS (10) and HAM-D (3)

ComparatorRapid-acting antidepressant
Depression thoughtsOTHER

EPD

ComparatorRapid-acting antidepressant
Quality of life and disabilityOTHER

Quality of life and disability

ComparatorRapid-acting antidepressant
Clinical and epidemiological factorsOTHER

Variables and categories

ComparatorRapid-acting antidepressant
Safety of ketamine IMDEVICE

Vital signs

ComparatorRapid-acting antidepressant
Tolerability of ketamine IMOTHER

UKU-SERS, YOUNG, CADSS and BPRS-12.

ComparatorRapid-acting antidepressant

Eligibility Criteria

Age18 Years - 40 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Diagnosis of TRD, according to clinical evaluation and confirmed by SCID-IV (Structured Clinical Interview for the DSM);
  • Moderate to severe intensity of the disease;
  • Female patients in fertile conditions should be using a clinically accepted contraceptive method (oral contraceptive and/or condom);
  • a. Blood test will be requested at the diagnostic stage and in case of clinical doubt as to the patient's gestational status,
  • Literate and able to understand the tasks requested;
  • With clinical comorbidities, however compensated;
  • Patients and/or legal representatives should understand the nature of the study and sign the Informed Consent Form.

You may not qualify if:

  • Imminent risk of suicide;
  • Patients with psychoactive substance dependence;
  • Intellectual deficit and psychotic symptoms;
  • Bipolar spectrum disorders and other primary psychiatric diagnoses;
  • Allergic to ketamine;
  • Glaucoma;
  • Treatment with reversible MAOI (monoamine oxidase inhibitor) in the week prior to visit 0;
  • Treatment with irreversible MAOI in two weeks prior to visit 0;
  • Fluoxetine treatment within 4 weeks prior to visit 0;
  • Treatment with others antidepressants;
  • Treatment with antipsychotics, lithium, benzodiazepines or other psychotropic drugs within 7 days prior to visit 0;
  • a. Lorazepam and zolpidem may be used;
  • Patients who become pregnant will be excluded from the study and referred for obstetric care.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

NĂºcleo de Pesquisas em SaĂºde Mental

Blumenau, Santa Catarina, 89.020-070, Brazil

Location

Related Publications (47)

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    PMID: 35935445DERIVED

MeSH Terms

Conditions

Depressive DisorderDepressive Disorder, Treatment-Resistant

Interventions

KetamineEscitalopramAripiprazoleQuality of Life

Condition Hierarchy (Ancestors)

Mood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPropylaminesAminesNitrilesBenzofuransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsPiperazinesHeterocyclic Compounds, 1-RingQuinolonesQuinolinesHealth StatusDemographyEpidemiologic MeasurementsPublic HealthEnvironment and Public Health

Study Officials

  • Ricardo A Moreno, MD, PhD

    Department and Institute of Psychiatry, University of Sao Paulo

    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
Model Details: Subjects will receive IM ketamine or IM saline applications as randomized. Applications will occur three times a week. It will be 4 weeks of IM application (12 initial applications). Injections will occur into the subjects' glutes (0.75 mg / kg). The ketamine group will use 2 placebo tablets and the parallel group escitalopram 15 mg and aripiprazole 5 mg. Thereafter, participants will receive weekly ketamine doses over 6 months as maintenance treatment. Research members will be submitted to Structured Clinical Interview for the DSM for diagnostic categorization and will be evaluated from other scales. Vital signs will be checked continuously for a period of 2 hours with each infusion. Patients will be observed in a quiet, comfortable room and subjected to medical monitoring for 2 hours. They will leave the environment in the company of a competent adult.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Study principal investigator

Study Record Dates

First Submitted

October 7, 2019

First Posted

January 21, 2020

Study Start

April 3, 2018

Primary Completion

June 3, 2020

Study Completion

April 3, 2021

Last Updated

January 21, 2020

Record last verified: 2019-12

Data Sharing

IPD Sharing
Will not share

Locations

BR(1)