Pharmacologic Treatment Augmentation in Chronic Depression

NCT06410599 | Recruiting Phase 2 DMC

• 2 other identifiers: 519/2019AMG12019-001692-37
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 2

Brief Summary

To enroll in this clinical trial, prospective participants must meet stringent criteria. The participants need to fall within the age range of 18 to 64 and exhibit chronic depression at therapy resistance stage 2. This stage signifies that the participants have undergone unsuccessful treatment with at least two different antidepressants, despite adequate dosage and duration. Moreover, the participants should have engaged in at least 12 sessions of psychotherapy without experiencing significant relief from depressive symptoms. Additionally, participants must demonstrate the cognitive capacity to provide informed consent. Upon expressing interest in the study and consenting to participate, individuals undergo a thorough screening process. This screening encompasses a comprehensive clinical interview to assess medical and psychiatric history, as well as various medical tests. These tests include physical examinations, blood draws (which may include pregnancy tests for female participants), and electrocardiograms (ECGs) to evaluate heart function. Following the screening, participants are randomly assigned to one of three different treatment groups (Ketamine +TAU; Ketamine+CBASP, Placebo+CBASP). The study protocol involves a combination of psychotherapeutic treatment and either ketamine infusions or placebo. Throughout the study period, participants are subject to regular data collection, including psychological assessments, blood samples, and magnetic resonance imaging (MRI) scans. Participants' responses to treatment, as well as any changes in symptoms or side effects, are closely monitored. After completing the study, participants are offered follow-up therapy as part of standard care. MRI scans are conducted to examine changes in brain activity associated with treatment response and depressive symptomatology, particularly focusing on alterations in neural circuitry and thought processes. Additionally, participants are encouraged to report any changes in medication regimen or other treatments received during the study period.

Conditions

Major Depressive Disorder

Keywords

Ketamine; CBASP; Augmentation; Combination therapy; Chronic depression; MDD

Outcome Measures

Primary Outcomes (1)

• Change of depressive symptoms assessed with Montgomery-Åsberg Depression Rating Scale (MADRS) between start and end of treatment in a group comparison

  Change of depressive symptoms (assessed with Montgomery-Åsberg Depression Rating Scale (MADRS), Schmidtke et al., 1988) between start of and six weeks after end of combination treatment (Δ t1-t3) in group 1 (ketamine plus CBASP) vs. group 2 (placebo plus CBASP) and in group 1 vs. group 3 (ketamine plus TAU). Lower scores indicate better treatment outcome.

  3 months after enrollment

Secondary Outcomes (2)

• Change of depressive symptoms assessed with Montgomery-Åsberg Depression Rating Scale (MADRS) in a group comparison

  6 months after enrollment

• Change of depressive symptoms of self-reported depressive symptoms (assessed with Beck-Depression-Inventory (BDI) in a group comparison

  3 months after enrollment

Other Outcomes (20)

• Pearson/Spearman correlation between actual number of single and group sessions and changes in depressive symptoms (as assessed by MADRS) in the different treatment groups.

  6 months after enrollment

• Pearson/Spearman correlation between actual session contents and changes in depressive symptoms (as assessed by MADRS) in the different treatment groups.

  6 months after enrollment

• Pearson/Spearman correlation between training level and changes (delta between timepoints) in depressive symptoms (as assessed by MADRS) in the different treatment groups.

  6 months after enrollment

Study Arms (3)

Ketamine+TAU

EXPERIMENTAL

Combination of ketamine hydrochloride (Ketamin Inresa 2 ml) and TAU during week 4 to 6. TAU (treatment as usual): standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements.

Drug: Ketamine; Behavioral: TAU

Placebo+CBASP

PLACEBO COMPARATOR

Combination of placebo and CBASP during week 4 to 6. CBASP: In addition to standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements, patients in the CBASP conditions receive one CBASP group session (50 min) per week for 12 weeks. The single sessions (one 50 min and one 25 min per week) contents are CBASP-specific.

Drug: Placebo; Behavioral: CBASP

Ketamine+CBASP

EXPERIMENTAL

Combination of ketamine hydrochloride (Ketamin Inresa 2 ml) and CBASP during week 4 to 6. CBASP: In addition to standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements, patients in the CBASP conditions receive one CBASP group session (50 min) per week for 12 weeks. The single sessions (one 50 min and one 25 min per week) contents are CBASP-specific.

Drug: Ketamine; Behavioral: CBASP

Interventions

Ketamine DRUG

Two ketamine hydrochloride (Ketamin Inresa 2 ml) infusions (interval 2-3 days) per week for three weeks, 6 infusions in total. Ketamine hydrochloride (Ketamin Inresa 2 ml) is applied continuously over a time span of 40 minutes with a subanesthetic dosage of 0.5 mg per kg body weight.

Also known as: Ketamine hydrochloride (Ketamin Inresa 2 ml)

Ketamine+CBASP; Ketamine+TAU

Placebo DRUG

Two times placebo (Isotone E NaCL 0.9 %) infusions (interval 2-3 days) per week for three weeks, 6 infusions in total. Placebo is applied continuously over a time span of 40 minutes.

Also known as: Saline solution: Fresenius Kabi Deutschland GmbH Isotone E NaCL 0.9 %

Placebo+CBASP

CBASP BEHAVIORAL

In addition to standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements, patients in the CBASP conditions receive one CBASP group session (50 min) per week for 12 weeks. The single sessions (one 50 min and one 25 min per week) contents are CBASP-specific.

Also known as: Cognitive Behavioral Analysis System of Psychotherapy

Ketamine+CBASP; Placebo+CBASP

TAU BEHAVIORAL

Standard ward psychotherapeutic program (group and single sessions) with cognitive behavioural, sociotherapeutic, occupational therapy and physiotherapeutic elements.

Also known as: Treatment as usual

Ketamine+TAU

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Diagnosis of chronic depression: recurrent depressive disorder, severe or moderate episodes (no full remission between the episodes according to DSM-IV-TR (Falkai et al., 2015) \[no distinct depressive symptoms for at least two months\]) or acute depressive episode lasting two or more years
• Treatment resistance stage 2 according to (Thase and Rush, 1997): Patient's symptoms fulfil the criteria of chronic depression listed above even after at least two appropriate treatment attempts with two antidepressant medicaments from two different effect categories
• Patient's symptoms fulfil the criteria of chronic depression listed above even after executing at least 12 sessions of psychotherapeutic treatment (psychoanalysis, depth psychology-based psychotherapy or cognitive behaviour therapy)
• Understand and voluntarily sign an informed consent document prior to any study related assessments/ procedures.
• Able to adhere to the study visit schedule and other protocol requirements.
• Females of childbearing potential (FCBP) must agree to utilize two reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact from study start until 28 days after the last infusion.
• Males must agree to use a latex condom during any sexual contact with FCBP from the first infusion until 65 days after the last infusion, even if the person has undergone a successful vasectomy to refrain from donating semen or sperm from the first infusion until 65 days after the last infusion.
• All subjects must agree to refrain from donating blood from the first infusion until 28 days after last infusion.
• All subjects must agree not to share medication.

You may not qualify if:

• Acute substance misuse as primary diagnosis (assessed by the Structured Clinical Interview for DSM-V (SKID, Wittchen et al., 1997))
• Neurologic disorders: Stroke, cerebral ischemia, tumor, cerebral infection, autoimmune disease (according to clinical interview)
• Disorders with increase of intracranial pressure, e. g. due to head injury (according to clinical interview)
• Circulatory disturbance in the brain (according to clinical interview)
• Pregnant or lactating females
• Participation in any clinical study or having taken any investigational therapy, which would interfere with the study's primary end point
• Epilepsy (according to clinical interview)
• History of hypersensitivity to an investigational medicinal product or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product (according to clinical interview)
• Pre-treatment with ketamine hydrochloride (Ketamin Inresa 2 ml) and/ or - CBASP (according to clinical interview)
• Not or insufficiently treated hypertonia (subject will be excluded if repeated measures (3 times/ day) show values greater than 150 mmHg systolic or 100 mmHg diastolic blood pressure or if a lifetime diagnosis of hypertonia is reported)
• Not or insufficiently treated hyperthyroidism (according to clinical interview)
• Heartache due to insufficient blood circulation (unstable angina pectoris) or heart muscle infarct (myocardia infarct) during the last six months (according to clinical interview)
• Increased intraocular pressure (glaucoma) and perforating eye injury (according to clinical interview)
• Interventions in the area of the upper respiratory passages (according to clinical interview)

Sponsors & Collaborators

• University Hospital Tuebingen: lead
• German Center for Mental Health: collaborator

Study Sites (2)

Universitätsklinikum Tübingen - Klinik für Psychiatrie und Psychotherapie

Tübingen, Baden-Würtemberg, 72070, Germany

RECRUITING

Universitätsklinikum Jena - Klinik für Psychiatrie und Psychotherapie

Jena, Thuringia, 07743, Germany

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ketamine; Therapeutics

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Martin Walter, Prof. Dr.

  Universitätsklinikum Jena - Klinik für Psychiatrie und Psychotherapie

  PRINCIPAL INVESTIGATOR

• Andreas J Fallgatter, Prof. Dr.

  Universitätsklinikum Tübingen - Klinik für Psychiatrie und Psychotherapie

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Walter, Prof. Dr.

CONTACT

+493641 9390101; martin.walter@med.uni-jena.de

Andreas J Fallgatter, Prof. Dr.

CONTACT

+4970712984858; andreas.fallgatter@med.uni-tuebingen.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: May 13, 2024
• Study Start: April 29, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 27, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (2)