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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Sodium lactate; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sylfa Fassassi,, MD; Phone Number: +41 21 314 31 11; Email: sylfa.fassassi@chuv.ch

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; intravenous, daily for 5 consecutive days
Experimental: Lactate	Drug: Sodium lactate; 2 mmol/kg, intravenous, daily for 5 consecutive days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility as assessed by the recruitment rate	% of patients eligible among the informed patients	12 weeks
Feasibility as assessed by the adherence rate	% of patients completing the study intervention period among randomized patients	12 weeks
Feasibility as assessed by the retention rate	% of drop-outs among randomized patients at 3 weeks, 6 weeks and 12 weeks	12 weeks
Feasibility as assessed by the data completion rate of the therapeutic effect measures	% of patients with completed Montgomery Asberg Depression Rating Scale (MADRS) questionnaire at 1, 2, 3, 6 and 12 weeks among randomized patients	12 weeks
Feasibility as assessed by estimates of the therapeutic effect size on Montgomery Asberg Depression Rating Scale (MADRS) score	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.	12 weeks
Feasibility as assessed by the blinding maintenance rate	% of patients with sustained blinding at week 1, 2, 3, 6 and 12	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anxiety	Generalized Anxiety Disorder - 7 items (GAD-7 score) ; minimum and maximum values : 0 - 21 ; Lower scores mean a better outcome	12 weeks
Perceived stress	Perceived Stress Scale (PSS score) ; minimum and maximum values : 0 - 40 ; Lower scores mean a better outcome	12 weeks
Insomnia	Insomnia Severity Index (ISI score) ; minimum and maximum values : 0 - 28 ; Lower scores mean a better outcome	12 weeks
Short term depression remission rate	Montgomery Asberg Depression Rating Scale (MADRS score < 7) ; minimum and maximum values : 0 - 60 ; Lower scores mean a better outcome	12 weeks
Hospitalization duration	Number of days of hospitalization	12 weeks

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois
• Collaborators: Fondation de Préfargier
• Investigators: Study Chair: Pierre Marquet, MD, Centre Hospitalier Universitaire Vaudois

Study record dates

Study Major Dates

• Study Start (Estimated): January 1, 2024
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: November 10, 2023
• First Submitted That Met QC Criteria: December 4, 2023
• First Posted (Estimated): December 13, 2023

Study Record Updates

• Last Update Posted (Estimated): December 13, 2023
• Last Update Submitted That Met QC Criteria: December 4, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Depression; Lactate; Antidepressant; Sodium lactate
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: Lac-MDD; 2023-01702 (Other Identifier: CER-VD)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No