Ketamine in treatment resistant major depression (TRD) -A placebo controlled, double blind, randomized trial of efficacy, safety and response prediction by resting state fMRI

Phase 2

Conditions: with healthy volunteers
F33
Recurrent depressive disorder

Registration Number: DRKS00003527

Lead Sponsor: Otto-von-Guericke University MagdeburgMedical Faculty

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Complete

Sex: All

Target Recruitment: 91

Inclusion Criteria

TRD subjects must satisfy the following criteria before entering the study:

• Male or female subjects between 18 and 55 years of age, inclusive.

• Subjects must fulfill ICD-10 for recurrent Major Depression (F 33) without psychotic
features, based on clinical assessment and confirmed by structured diagnostic interview.

• Subjects must have an initial score of at least 16 on the 21-item HAMD at screen and at
baseline of study phase I.

• Current history of lack of response to two adequate antidepressant trials (may be from
the same chemical class) operationally defined using the Antidepressant Treatment History Form (ATHF).

• Current major depressive episode of at least 4 weeks duration.

Both healthy controls and TRD subjects must fulfill the following criteria:

• Women of childbearing potential must have a negative pregnancy test on the day of each
scan, prior to participating in MRI imaging part of the study.

• Healthy or medically stable on the basis of clinical laboratory tests performed at
screening.

• Healthy or medically stable on the basis of physical examination, medical history, vital signs (including
orthostasis test) or 12 lead ECG (including QTcB <470 ms) at Screening. Minor deviations in ECG, which are not considered to be of clinical significance to the investigator are acceptable.

• Willing to adhere to the prohibitions and restrictions specified in this protocol.

• Subjects must have signed an informed consent document indicating that they
understand the purpose of and procedures required for the study and are willing to participate in the study.

Exclusion Criteria

Potential TRD subjects who meet any of the following criteria will be excluded from participating in the study:

• Current or past history of psychotic features or a diagnosis of Schizophrenia or any other
psychotic disorder as defined in the ICD-10.

Potential healthy control subjects who meet any of the following criteria will be excluded from participating in the study:

• Current or past history of psychotic features or a diagnosis of any psychiatric disorder as defined in the ICD-10.

Both TRD subjects and healthy control subjects who meet any of the following criteria will be excluded from participating in the study:

• Subjects with a history of drug or alcohol dependency or abuse within the preceding 6 months.

• Female subjects who are either pregnant or nursing.

• Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory,
cardiovascular (including ischemic heart disease), endocrinologic, neurologic,
immunologic, or hematologic disease.

• Subjects with uncorrected hypothyroidism or hyperthyroidism.

• Subjects with one or more seizures without a clear and resolved etiology.

• Presence of metallic (ferromagnetic) implants (heart pacemaker, aneurysm clips) or
tattoos.

• Subjects with any medical illness likely to alter brain morphology and/or physiology
(uncontrolled hypertension, diabetes) will be excluded.

• Treatment with a reversible MAOI within 4 weeks prior to baseline assessment.

• Treatment with clozapine or ECT within 3 months prior to baseline assessment.

• Judged clinically to be at serious suicidal risk.

• Drinks, on average, more than 8 cups of tea/coffee/cocoa/cola per day.

• Use of energy drinks within 3 days before the baseline assessment and during the
duration of the study.

• Clinically significant acute illness within 7 days prior to study drug administration.

• Clinically significant history of drug and/or food allergies.

• Donation of 1 or more units (approximately 450 mL) of blood or acute loss of an
equivalent amount of blood within 90 days prior to study drug administration.

• Participation in another clinical trial (drug, medical device): Have received an experimental drug or used an experimental medical device within 90
days before the planned start of treatment.

Study & Design

Study Type: interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Improvement on HAMD (Hamilton rating scale for depression) scores in patients, 24 hours after ketamine infusion.

Secondary Outcome Measures

Name	Time	Method
Secondary endpoint 1: <br>Predictive value of regional homogeneity (ReHo), glutamine concentration and functional connectivity (FC) of pgACC for treatment response to ketamine in patients. <br><br>Secondary endpoint 2:<br>Greater changes of glutamine concentration after ketamine infusion acutely and after 24 hours compared to placebo<br><br>

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