Clinical trial NCT06168175: Feasibility of Conducting a Clinical Trial Assessing Efficacy of Lactate as Adjunctive Therapy in Patients With Major Depressive Disorder
Official title: A Feasibility Single-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Feasibility of Conducting a Full-scale Randomized Controlled Trial (RCT) Assessing Efficacy of Lactate as Adjunctive Therapy in Hospitalized Patients With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Major Depressive Disorder
Keywords: Sodium lactate
Depression
Antidepressant
Lactate
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
Collaborators: name: Fondation de Préfargier
First posted: 2023-12-13
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to test the efficacy of lactate (a natural substance) in combination with standard antidepressant treatment, in patients hospitalized for a major depressive episode.

The main question\[s\] it aims to answer are:

* does lactate diminishes depression severity when administered in combination with antidepressant ?
* is it feasible to test lactate treatment in a large-scale clinical trial ? Participants will receive lactate intravenously daily (20 min infusion) for 5 days during hospitalisation (together with the standard antidepressant treatment).

Researchers will compare with a group receiving a placebo instead of lactate to see if lactate has antidepressant effects.

Detailed description: In case of major depressive disorder (MDD), antidepressant medications are prescribed as standard treatment. The commonly used antidepressants have a delayed onset of therapeutic actions, many side effects and limited efficacy. In this regard, about 30-50% of MDD patients are unresponsive to any currently approved pharmacological treatment, emphasizing the need for novel types of drugs to treat major depression.

Several animal studies have shown that lactate, a substance naturally present in the body, has antidepressant effects.

The aim of this single-center study is to evaluate the feasibility of conducting a future large-scale clinical trial testing the efficacy of "sodium lactate" as an adjunctive treatment to a standardly prescribed antidepressant.

The study is recruiting patients hospitalized for a major depressive episode. Participants are assigned randomly to the "sodium lactate" group or the "placebo" group. The study treatment will be administered intravenously daily (2mmol/kg) for 5 days during hospitalization, in addition to standard antidepressant treatment. Patients will be followed during hospitalization and then on an outpatient basis at 6 and 12 weeks. The therapeutic effect of sodium lactate will be assessed with the MADRS score (depression severity scale) at 1, 2, 3, 6 and 12 weeks. Recruitment, adherence, retention, data completion and blinding maintenance rates will also be assessed to evaluate the feasibility. The effect on anxiety, perceived stress, insomnia, short-term depression remission rate, blood lactate level and length of hospitalization will also be evaluated.

Eligibility criteria: Inclusion Criteria:

* Study consent signed
* 18 ≤ age ≤ 65 years old
* Fluent in french
* Recently (no more than 1 week) hospitalized for a primary diagnosis of MDD
* Current major depressive episode as defined by DSM-5
* Current MADRS score ≥18
* Total number of MDD acute episodes ≤ 3
* Total number of psychiatric medications ≤ 3 at admission
* Total number of any medication ≤ 4 at admission
* No signs or evidence indicating difficult intravenous access
* Willing to hold a peripheral blood catheter for 5 days

Exclusion Criteria:

* Bipolar depression
* History of panic attacks
* Severe substance use disorders according to DSM-5-TR criteria
* Conditions predisposing to hypernatremia such as:

  * adrenocortical insufficiency,
  * diabetes type 1 and insulin-dependent type 2
  * extensive tissue injury
* Known severe renal insufficiency
* Known hepatic insufficiency (impaired lactate metabolism)
* Known history of heart failure
* Known history of Chronnic Obstructive Pulmonary Disease or respiratory failure
* Known hypersentitivity to lactate
* Hypernatremia with Na+ \> 150 mmol/L (confirmed on 2 blood withdrawals)
* Blood osmolality \> 320 mmol/kg H2O
* Hyperlactatemia \> 2 mmol/l
* Pregnant or lactating
* Forbiden medications : Lithium
* Participation to other clinical trials
* Any medical conditions that could jeopardize patient's health in case of study participation according to the investigator
* Inability to give informed consent (without capacity for discernment) as evaluated by the psychiatrist investigator or by by a delegated physician.

Primary outcomes:
measure: Feasibility as assessed by the recruitment rate
timeFrame: 12 weeks
measure: Feasibility as assessed by the adherence rate
timeFrame: 12 weeks
measure: Feasibility as assessed by the retention rate
timeFrame: 12 weeks
measure: Feasibility as assessed by the data completion rate of the therapeutic effect measures
timeFrame: 12 weeks
measure: Feasibility as assessed by estimates of the therapeutic effect size on Montgomery Asberg Depression Rating Scale (MADRS) score
timeFrame: 12 weeks
measure: Feasibility as assessed by the blinding maintenance rate
timeFrame: 12 weeks
Secondary outcomes:
measure: Anxiety
timeFrame: 12 weeks
measure: Perceived stress
timeFrame: 12 weeks
measure: Insomnia
timeFrame: 12 weeks
measure: Short term depression remission rate
timeFrame: 12 weeks
measure: Hospitalization duration
timeFrame: 12 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Centre Hospitalier Universitaire Vaudois
name: Pierre Marquet, MD
role: STUDY_CHAIR
References: