Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents

NCT06147050 | Not Yet Recruiting Phase 3

• 1 other identifier: Metformin in Long COVID
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Long Covid is a multisystem condition comprising often severe symptoms that follow a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Long COVID often manifests as fatigue and neurocognitive impairment (also referred to as 'brain fog'). Based on two systematic reviews of Covid-19 cases in neonates, children and adolescents under 19 years of age, fatigue caused by Long Covid can persist for years and can lead to work disability and labour shortages, posing a public health emergency with lasting health, mental, and economic impacts. To date, no treatment has shown to be broadly effective for the treatment of Long Covid. An experimental study has demonstrated that metformin, a common diabetes drug, might reduce the incidence of long COVID if given during the acute phase of COVID-19. The study, however, did not look at whether metformin would be effective as a treatment for those who already have long COVID. It also did not report the results by age groups, so it is not clear if the effect of metformin differs for people younger than 35 years of age. Therefore, a pilot, adaptive randomized controlled trial, which will evaluate the feasibility of conducting a large platform trial and will also evaluate the efficacy and safety of using metformin (versus placebo, a look-alike substance with no active ingredient) in managing fatigue in long COVID adolescent patients with persistent (long term) features of fatigue (chronic fatigue syndrome) has been proposed.

Conditions

Long COVID

Keywords

Long COVID; Metformin; Chronic Fatigue Syndrome

Outcome Measures

Primary Outcomes (1)

• Mean Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) score at 90 days post-randomization

  The PedsQL-MFS questionnaire is a validated instrument that is designed to measure fatigue in the pediatric population. The questionnaire is validated for different age groups, including adolescents. The questionnaire is comprised of three dimensions including general fatigue, sleep/rest fatigue, and cognitive fatigue. It includes 18 likert-type questions. It is scored from 0 to 100, with a higher score representing lower levels of fatigue. A score below 75 will be used to represent clinically significant pain

  90 days post-randomization

Secondary Outcomes (9)

• Mean PedsQL-MFS score at 30 days post-randomization

  30 days post-randomization

• Mean PedsQL-MFS score at 60 days post-randomization

  60 days post-randomization

• Mean Chalder Fatigue Scale (CFS) score at 30 days post-randomization

  30 days post-randomization

• Mean CFS score at 60 days post-randomization

  60 days post-randomization

• Mean CFS score at 90 days post-randomization

  90 days post-randomization

Study Arms (2)

Metformin

EXPERIMENTAL

Drug: Metformin * Patients assigned to the metformin arm will receive a 500-mg dose of metformin extended-release formulation twice daily for a period of 30 days * 500 mg extended-release tablet (Twice Daily) * Participants will be randomised in a 1:1 ratio to receive 1 dose of Metformin or Placebo on same day as randomisation

Drug: Metformin

Placebo Control

PLACEBO COMPARATOR

Other: Placebo control • Participants will be randomised in a 1:1 ratio to receive 1 dose of Metformin or Placebo on same day as randomisation

Other: Placebo

Interventions

Metformin DRUG

Metformin is an FDA-approved antidiabetic agent that manages high blood sugar levels in type 2 diabetes patients. However, emerging evidence may suggest a benefit to COVID recovery.

Metformin

Placebo OTHER

Patients will receive matching placebo control twice daily.

Placebo Control

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 10 to 18 years at time of screening
• Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where locally and nationally approved)
• Previous confirmed case of SARS-CoV-2 infection (e.g., communicates that they previously had a positive nucleic acid amplification test or had a positive professional use or self-test SARS-CoV-2 rapid antigen diagnostic test)
• New or worsening symptoms since acute COVID-19 illness that have persisted for a duration of at least 90 days but less than 365 days
• Not currently hospitalized or requiring hospitalization
• Patients with childbearing potential or with partners of childbearing potential must agree to use adequate methods of contraception during the trial and through 90 days of follow-up
• Able to complete the questionnaires
• Reports moderate to severe fatigue, defined as a score of 75 or lower on the PedsQL-MFS
• Fatigue symptoms have been present for at least 90 days since time of COVID-19 infection
• Fatigue symptoms are not attributable to another cause (in opinion of investigator)
• Willingness to follow the trial procedures

You may not qualify if:

• Known active acute SARS-CoV-2 infection
• Known prior diagnosis of myalgic encephalomyelitis/chronic fatigue syndrome, not related to SARS-CoV-2 infection
• Known pre-existing dysautonomia, not related to SARS-CoV-2 infection
• Diabetes
• Known stroke within 3 months of screening
• Known severe anemia, defined as \< 8 g/dL21
• Known diagnosis of Lyme disease
• Any non-marijuana illicit drug use within 30 days prior to informed consent
• Pregnancy or breastfeeding
• Current co-morbid psychiatric disorder (e.g. clinical depression, anxiety, sleep disorder, eating disorder, substance abuse) that is uncontrolled and associated with significant symptoms or that requires a prohibited medication
• Taking medications with known side effect of chronic fatigue
• Contraindications to metformin
• Patients with a history of seizures may participate if they have not occurred in the last 60 days and are stable, under pharmacological control
• Any condition that would make the patient, in the opinion of the investigator, unsuitable for the trial

Sponsors & Collaborators

• Purpose Life Sciences: lead

Study Sites (1)

Suite No 301, Al-Sehat Centre, Adj Regent Plaza Hotel Rafiqui Shaheed Road

Karachi, Sindh, 75510, Pakistan

Location

Related Publications (2)

• Xie Y, Bowe B, Al-Aly Z. Burdens of post-acute sequelae of COVID-19 by severity of acute infection, demographics and health status. Nat Commun. 2021 Nov 12;12(1):6571. doi: 10.1038/s41467-021-26513-3.

  PMID: 34772922 BACKGROUND

• Al-Aly Z, Xie Y, Bowe B. High-dimensional characterization of post-acute sequelae of COVID-19. Nature. 2021 Jun;594(7862):259-264. doi: 10.1038/s41586-021-03553-9. Epub 2021 Apr 22.

  PMID: 33887749 BACKGROUND

MeSH Terms

Conditions

Post-Acute COVID-19 Syndrome; Fatigue Syndrome, Chronic

Interventions

Metformin

Condition Hierarchy (Ancestors)

COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Muscular Diseases; Musculoskeletal Diseases; Encephalomyelitis; Neuroinflammatory Diseases; Nervous System Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Zamir Hussain Suhag, MBBS, FCPS

  Technical Director of Trust in Vaccines & Immunization, Pakistan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zamir Hussain Suhag, MBBS, FCPS

CONTACT

(+92)-300-2018880; zamir.suhag@tvi.org.pk

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Technical Director of Trust in Vaccines & Immunization, Pakistan

Study Record Dates

• First Submitted: November 24, 2023
• First Posted: November 27, 2023
• Study Start: April 1, 2024
• Primary Completion: October 1, 2024
• Study Completion: December 1, 2024
• Last Updated: March 4, 2024

Record last verified: 2024-02

Locations

PA (1)