Evaluation of Ketamine Hydrochloride and CBASP in the Augmentation of Pharmacologic Treatment for Chronic Depression: A Randomized, Double-Blind, Phase II Trial
- Trial ID
- 2024-512478-86-00
- Protocol
- Ketamin plus CBASP
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized, controlled, double-blinded, phase II study is to evaluate the **reduction of depressive symptoms** in patients with chronic depression. This is assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS) over a specified period. The study compares the efficacy of a combination treatment of ketamine plus Cognitive Behavioral Analysis System of Psychotherapy (CBASP) against a placebo plus CBASP, as well as ketamine plus treatment as usual (TAU). The clinical relevance of this objective lies in its potential to enhance treatment strategies for chronic depression, a condition often resistant to standard therapies.
Participants
The clinical trial focuses on individuals diagnosed with **chronic depression**, specifically targeting those aged 18 to 64 years. The study population includes both male and female participants, with a particular emphasis on those who have experienced recurrent depressive disorder with severe or moderate episodes, or an acute depressive episode lasting two or more years. Participants are required to have demonstrated treatment resistance, defined as having persistent symptoms despite at least two appropriate treatment attempts with different antidepressant medications and at least 12 sessions of psychotherapeutic treatment. The trial involves a vulnerable population, and participants must have the ability to understand and voluntarily sign the informed consent form, as well as adhere to the study visit schedule and other protocol requirements. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity.
Plans and Procedures
The clinical trial is designed as a **randomized, controlled, double-blind, phase II study** aimed at evaluating the efficacy of pharmacologic treatment augmentation in individuals diagnosed with **chronic depression**. The primary objective is to assess the reduction of depressive symptoms using the Montgomery–Åsberg Depression Rating Scale (MADRS) over a specified period. The trial will compare the effects of ketamine plus Cognitive Behavioral Analysis System of Psychotherapy (CBASP) against placebo plus CBASP, and ketamine plus treatment as usual (TAU). The study is expected to commence recruitment on March 27, 2024, and conclude by May 3, 2027.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-64 years), diagnosis of chronic depression, and treatment resistance. The trial will involve multiple follow-up visits to monitor progress and assess treatment efficacy, with the end-of-study visit marking the conclusion of participant involvement. The total duration of participant involvement is anticipated to be six weeks, aligning with the treatment period.
Participants will be randomly assigned to one of the treatment groups, ensuring the double-blind nature of the study, where neither the participants nor the treatment team will know the specific treatment allocation. The trial will employ **intravenous infusion** of the investigational products, with ketamine hydrochloride and sodium chloride being the active substances under investigation. The maximum daily dose is set at 0.5 mg/kg, with a total dose not exceeding 6 mg/kg over the treatment period.
Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse reactions to the treatment, or withdrawal of consent by the participant. The trial is structured to maintain rigorous scientific standards, ensuring the reliability and validity of the findings. The study's design and methodology are aligned with ethical guidelines and regulatory requirements, providing a robust framework for evaluating the potential benefits of the treatment regimen in managing chronic depression.
Treatment
The clinical trial involves the administration of **ketamine hydrochloride** as an experimental treatment. The pharmaceutical form of this medication is a **solution for injection**, specifically marketed as "Ketamin Inresa 2 ml, 50 mg/ml Injektionslösung, Ketaminhydrochlorid" by INRESA ARZNEIMITTEL GMBH. The active substance, ketamine hydrochloride, is of chemical origin. The medication is administered via **intravenous infusion**. The dosing regimen includes a maximum daily dose of 0.5 mg/kg and a maximum total dose of 6 mg/kg over a treatment period of up to 6 weeks. This treatment is utilized in the context of augmenting pharmacologic therapy in patients with chronic depression.
In addition to the experimental treatment, the trial employs a **placebo** as a comparator. The placebo is an **isotonic sodium chloride solution**, marketed as "Isotonische Kochsalzlösung Fresenius, Infusionslösung" by FRESENIUS KABI DEUTSCHLAND GMBH. This solution is also administered as a **solution for infusion** via intravenous infusion. The placebo serves as a control to evaluate the efficacy of the ketamine treatment in reducing depressive symptoms. The administration schedule and dosing for the placebo mirror those of the ketamine treatment to maintain blinding and consistency within the study protocol.
Efficacy
Efficacy in this clinical trial will be assessed by evaluating the reduction of depressive symptoms in patients with chronic depression. The primary endpoint for efficacy evaluation is the change in depressive symptoms, which will be measured using the **Montgomery–Åsberg Depression Rating Scale (MADRS)**. This is a standardized and widely used clinician rating scale designed to assess the severity of depressive episodes. The MADRS assessments will be conducted by a rater who is independent of the treatment team and blind to the treatment condition, ensuring objectivity in the evaluation process.
The trial aims to compare the efficacy of ketamine combined with Cognitive Behavioral Analysis System of Psychotherapy (CBASP) against a placebo combined with CBASP, as well as ketamine combined with Treatment As Usual (TAU). The primary objective is to observe the reduction in depressive symptoms from the start of the treatment to six weeks after the end of the combination treatment. The trial is structured as a randomized, controlled, double-blinded, phase II study, focusing on pharmacologic treatment augmentation in chronic depression.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age 18-7064 at the time of study inclusion• 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 & 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)• Ability to give approval; Ability to understand and voluntarily sign the informed consent form• Ability to adhere to the study visit schedule and other protocol requirements• 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.• Contraception:Male must agree to use a condom during any heterosexual contact with Females of Childbearing Potential (FCBP) from the first infusion until 65 days after the last infusion, even if he has undergone a successful vasectomy, as well as to not donate semen or sperm during this time period.FCBP must agree to use two one reliable forms of contraception simultaneously or practice complete abstinence from heterosexual contact from study start until 28 days after the last infusion.Definition of Females of Childbearing Potential (FCBP)A FCBP is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months).
Exclusion Criteria
- Current or previous diagnosis of acute substance misuse disorder, except abstinence of at least 3 months. Low dose dependencies of benzodiazepines can be accepted by decision of the study physician.• Neurologic disorders: Stroke, cerebral ischemia, tumor, cerebral infection, autoimmune disease• Disorders with increase of intracranial pressure, e.g. due to head injury• Circulatory disturbance in the brain• 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• 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• Pretreatment with ketamine hydrochloride (Ketamin Inresa 2 ml) and/ or CBASP• Inability to tolerate CBASP (e.g., organic brain disorders, severe cognitive deficits)• Not or insufficiently treated hypertonia (arterial hypertonia – systolic/ diastolic blood pressure higher than 150/ 100 mmHg at rest)• Not or insufficiently treated hyperthyrodism• Heartache due to insufficient blood circulation (unstable angina pectoris) or heart muscle infarct (myocard infarct) during the last six months• Increased intraocular pressure (glaucoma) and perforating eye injury• Interventions in the area of the upper respiratory passages that currently prevent or impede intubation ability
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Germany | Recruiting | 27 Mar 2024 | 60 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Ketamin Inresa 2 ml
50 mg/ml Injektionslösung
Ketaminhydrochlorid | Test | INJEKTIONSLÖSUNG | INTRAVENIOUS INFUSION | 0.5 | 6 | PRD7673130 |
SODIUM CHLORIDE | Placebo | — | INTRAVENOUS INFUSION | 50 | 3 | SUB12581MIG |