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Feasibility of Conducting a Clinical Trial Assessing Efficacy of Lactate as Adjunctive Therapy in Patients With Major Depressive Disorder

Phase 2
Not yet recruiting
Conditions
Major Depressive Disorder
Interventions
Registration Number
NCT06168175
Lead Sponsor
Centre Hospitalier Universitaire Vaudois
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
46
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlacebo-
LactateSodium lactate-
Primary Outcome Measures
NameTimeMethod
Feasibility as assessed by the recruitment rate12 weeks

% of patients eligible among the informed patients

Feasibility as assessed by the blinding maintenance rate12 weeks

% of patients with sustained blinding at week 1, 2, 3, 6 and 12

Feasibility as assessed by estimates of the therapeutic effect size on Montgomery Asberg Depression Rating Scale (MADRS) score12 weeks

Estimate of mean difference on the change in MADRS score from baseline to week 1, 2, 3, 6 and 12 between patients randomized in lactate arm and in placebo arm, as well as their associated standard deviation.

Feasibility as assessed by the adherence rate12 weeks

% of patients completing the study intervention period among randomized patients

Feasibility as assessed by the retention rate12 weeks

% of drop-outs among randomized patients at 3 weeks, 6 weeks and 12 weeks

Feasibility as assessed by the data completion rate of the therapeutic effect measures12 weeks

% of patients with completed Montgomery Asberg Depression Rating Scale (MADRS) questionnaire at 1, 2, 3, 6 and 12 weeks among randomized patients

Secondary Outcome Measures
NameTimeMethod
Insomnia12 weeks

Insomnia Severity Index (ISI score) ; minimum and maximum values : 0 - 28 ; Lower scores mean a better outcome

Anxiety12 weeks

Generalized Anxiety Disorder - 7 items (GAD-7 score) ; minimum and maximum values : 0 - 21 ; Lower scores mean a better outcome

Perceived stress12 weeks

Perceived Stress Scale (PSS score) ; minimum and maximum values : 0 - 40 ; Lower scores mean a better outcome

Short term depression remission rate12 weeks

Montgomery Asberg Depression Rating Scale (MADRS score \< 7) ; minimum and maximum values : 0 - 60 ; Lower scores mean a better outcome

Hospitalization duration12 weeks

Number of days of hospitalization

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