Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19. (COVMENT)

Randomized, Double-blind, Placebo-controlled Trial of the Efficacy and Safety of Tianeptine in the Treatment of Covid Fog Symptoms in Patients After COVID-19 With the Study of the Pathophysiology of the Phenomenon Using Positron Emission Tomography, Biochemical, Immunological and Electrophysiological Parameters.

COVID-19 is associated with a high risk of complications from the central nervous system. Syndrome of cognitive disorders- in terms of memory, attention or executive functions among COVID-19 convalescents is often called brain fog (covid fog - CF). CF leads to psychomotor retardation and chronic fatigue syndrome, resulting in poor functioning and low quality of life. CF may affect up to 81% of patients after COVID-19.

Prevalence of CF may be even greater among patients with severe forms of COVID-19. In the preliminary assessment authors found that 83% of COVID-19 inpatients had at least mild cognitive impairment. Moreover, SARS-CoV-2 infection is associated with higher incidence of depression and anxiety disorders. CF pathogenesis is not fully understood. There exist no strict diagnostic criteria for it, as well as no therapeutic recommendations. Health care systems of many countries, including Poland, lack therapeutic programs addressed at patients with CF. Tianeptine may be a drug with potentially beneficial effects in CF. Neuroprotective, antidepressive, sleep-improving and anxiolytic properties of tianeptine allow it to choose as a candidate for CF amelioration. There is also data supporting the thesis that patients with CF may benefit from short-term group therapy. It has been proven to improve quality of life, reduce stress, and improve cognitive function in non-MC cognitive disorders.

Expected research results: A database will be created from the collected clinical, laboratory and additional data. Statistical models will be created to predict: the duration of disorders, response to therapy, the final result of treatment. Among the markers of CNS damage, those which correlates with the patient's condition will be selected.

The study will allow to estimate the prevalence of CF in the population. PET-CT and auditory evoked potentials also will be used to expand knowledge in the field of CF.

Based on the existing data, an improvement is expected in all investigated participants as a result of rehabilitation and psychotherapy.

Additional improvement is expected in the tianeptine group. Improvement will be defined as: reduction in the severity of anxiety and depression disorders, reduction in the severity of cognitive disorders, improvement in the quality of life. The results will be used to develop a new diagnostic and therapeutic pathway and a comprehensive intervention program in CF.

Study Overview

• Status: Recruiting
• Conditions: Nervous System Diseases
• Intervention / Treatment: Drug: Tianeptine; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 140
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Anna Klimkiewicz, MD, PhD; Phone Number: +48695723984; Email: aklimkiewicz@wim.mil.pl

Study Locations

• Poland
  • Warsaw, Poland
    • Recruiting
    • Anna Klimkiewicz
    • Contact: Anna Klimkiewicz, MD, PhD; Phone Number: +48695723984; Email: aklimkiewicz@wim.mil.pl

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Written informed consent from the patient to participate in the clinical trial.
• Age ≥ 18 years.
• History of COVID-19 infection confirmed by a positive SARS-CoV-2 test result by RT- PCR or positive antigen test.
• Subjective patient-reported cognitive decline after COVID-19 infection at Screening.
• Cognitive dysfunction found at Screening, defined by the Montreal Scale for the Assessment of Cognitive Function (MoCA) as a score of less than 26.
• Use of effective contraception by women of childbearing potential.

Exclusion Criteria:

• Hypersensitivity to tianeptine.
• Hypersensitivity to fluorodesoxyglucose (FDG).
• History of allergy to drugs or other substances, which, in the Investigator's opinion, is a contraindication to participation in the study.
• History of stroke.
• Ever undergone and planned brain surgery at the time of the study.
• Previously diagnosed organic damage to the central nervous system.
• Diagnosed organic mental disorder.
• Diagnosed bipolar affective disorder.
• Diagnosed psychotic disorder.
• History of active depressive episode, including those diagnosed at the time of study eligibility, requiring antidepressant treatment.
• Diagnosed mental retardation.
• Bipolar affective disorder in a first-degree relative.
• Uncontrolled diabetes mellitus.
• Severe renal failure with eGFR < 30ml/min/1.73 m2.
• cirrhosis of liver Severe liver cirrhosis (Child-Pugh class C ).
• Claustrophobia.
• Diagnosed chronic diseases that significantly worsen the patient's prognosis and quality of life, which, in the Investigator's opinion, may adversely affect the patient's participation in the study.
• Active or past malignancy within the past 5 years, except for basal cell carcinoma of the skin and cervical cancer in situ in patients who have received radical treatment.
• Active viral, bacterial, fungal, tuberculous, or parasitic infection.
• History or presence of other relevant diseases which, in the Investigator's opinion, is a contraindication to participation in the study.
• Positive pregnancy test performed on women of childbearing potential at screening or Visit 1.

• Taking medications:

  1. Non-selective MAO inhibitors within 14 days prior to screening,
  2. Mianserin during screening.
• Significant difficulty with peripheral venous cannulation.
• Positive history of alcohol, drug, and psychoactive abuse/dependence.
• Pregnancy or planning a pregnancy during the study period.
• Breastfeeding or planning to breastfeed during the study period.
• Current participation in another clinical trial.
• Lack of patient compliance.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stady group; The study group will receive oral tianeptine in a dose of 3x 12.5 mg per day (patients younger than 70) or 2x 12.5 mg per day (patients older than 70) for 16 weeks. In addition, the subjects will participate in group psychotherapy and neurological rehabilitation.	Drug: Tianeptine; Tianesal 12,5mg
Placebo Comparator: Control group; The control group will receive oral placebo in a dose of 3x 12.5 mg per day (patients younger than 70) or 2x 12.5 mg per day (patients older than 70) for 16 weeks. In addition, the subjects will participate in group psychotherapy and neurological rehabilitation.	Drug: Placebo; application as in the control group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in covid fog symptoms	Improvement in covid fog symptoms at week 16 after randomization defined as a 2 point improvement in MoCA score.	16 week after randomization

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
improving cognitive function	Complete resolution of covid fog symptoms at week 16 after randomization defined as normalization of MoCA scale score (MoCA = 26 - 30 points).	16 week after randomization
Change in brain metabolic activity	Change in brain metabolic activity as assessed by PET-CT at week 16 after randomization.	16 week after randomization

Collaborators and Investigators

• Sponsor: Military Institute od Medicine National Research Institute
• Collaborators: ABM Industries

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2023
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): October 31, 2027

Study Registration Dates

• First Submitted: August 24, 2023
• First Submitted That Met QC Criteria: August 24, 2023
• First Posted (Actual): August 25, 2023

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: confusion; COVID-19; memory problems; headaches; brain fog; poor concentration; Covid Fog; COVID-19 brain fog; lack of mental clarity
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Nervous System Diseases; Psychotropic Drugs; Antidepressive Agents; Antidepressive Agents, Tricyclic; Tianeptine
• Other Study ID Numbers: ABM/COVMENT/2021; 2022-000893-25 (EudraCT Number)

Drug and device information, study documents

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