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Long COVIDPhase 3REVIVENCT06147050

Effect of Metformin in Reducing Fatigue in Long COVID in Adolescents

A Phase 3 study testing Metformin in people with Long COVID, run by Purpose Life Sciences at 1 site in Pakistan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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'). Read more about this study

Who is it for?
Ages 10 to 18 years
Conditions the study is for
Long COVID
What is being tested?
Metformin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
16 participants
Where
1 sitePakistan
Study dates
Apr 2024to Dec 2024
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Zamir Hussain Suhag, MBBS, FCPS contact

(+92)-300-2018880

zamir.suhag@tvi.org.pk

Pakistan1 site
  • Suite No 301, Al-Sehat Centre, Adj Regent Plaza Hotel Rafiqui Shaheed Road

    Karachi, Sindh, 75510

Other trials in Pakistan

About this study

Official title: Pilot Study of an Adaptive, Double-blind, Randomized, Placebo-controlled Study to Evaluate the Effect of Metformin in Reducing Fatigue in Long COVID Adolescent Patients With Chronic Fatigue Syndrome

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.

Read the detailed description

Shortly after the beginning of the COVID-19 global pandemic, reports emerged showing that some individuals infected with SARS-CoV-2 developed persistent symptoms and new health problems that arose long after the acute phase of infection and could not be explained by other factors. The patient community who first recognized and reported this new syndrome used the term 'long COVID' to describe the post-acute and chronic sequelae of SARS-CoV-2 infection. Long COVID (sometimes referred to as 'post-acute sequelae of COVID-19') is a multisystem condition comprising often severe symptoms that follow a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This condition affects all individuals ubiquitously regardless of their race, age, gender, baseline health status and the severity of their initial COVID infection. As reported by the two systematic reviews of the total COVID-19 cases of neonates, children, and adolescents aged less than 19 years since the start of the pandemic, the persistent clinical features spectrum of long COVID is wide with fatigue having the second highest percentage of persistent long COVID symptoms within this age group. Long COVID symptoms can last for years, particularly in cases for chronic fatigue syndrome/dysautonomia which can be lifelong. Therefore, significant proportions of individuals have been unable to return to work which has even to led to labour shortages. Consequently, long COVID is considered a public health emergency that can have lasting health, mental health, and economic sequelae.

Since, the clinical trials done so far have not been prioritized to understand the diagnosis, treatment, and prevention in marginalized populations such as adolescents and because of the high disability associated with this condition, research targeting this age group for the management of long COVID is needed. There are currently no approved therapies for long COVID; however, treatments for certain components have been effective for subsets of populations. Metformin has been proposed in this study as a potential avenue for the management of chronic fatigue that is associated with long COVID. It has clinical benefits when used as an outpatient treatment for COVID-19 and is globally available, has a low-cost, and is safe. A study that was conducted recently had reported that its use in patients infected with COVID could reduce the incidence of long COVID. However, since this study had only focused on older individuals who were already infected with COVID, a pilot trial evaluating the efficacy and safety of metformin in younger individuals with long COVID is warranted.

Therefore, a pilot, adaptive randomized controlled trial has been proposed, which will evaluate the feasibility of conducting a large platform trial and will also evaluate the efficacy and safety of using metformin versus placebo, (since there's no approved therapy for it) in managing fatigue in long COVID adolescent patients with persistent features of fatigue (chronic fatigue syndrome).

Conditions
Long COVID
Being tested
Metformin, Placebo
Keywords
Long COVID, Metformin, Chronic Fatigue Syndrome
Medical subject headings
Post-Acute COVID-19 Syndrome, Fatigue Syndrome, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    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.

  • PlaceboOther

    Patients will receive matching placebo control twice daily.

Study groups in NCT06147050
Study groupRoleWhat they receive
MetforminExperimentalDrug: 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
Receives: Drug: Metformin
Placebo ControlPlacebo comparatorOther: Placebo control • Participants will be randomised in a 1:1 ratio to receive 1 dose of Metformin or Placebo on same day as randomisation
Receives: Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 90 days post-randomization

Secondary outcomes (9)
  1. Mean PedsQL-MFS score at 30 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

    Measured: 30 days post-randomization

  2. Mean PedsQL-MFS score at 60 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

    Measured: 60 days post-randomization

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

    The CFS includes 11 likert-type questions that ask about feeling tired or lacking in energy. the questionnaire is scored from 0 to 33, with higher scores representing a higher level of fatigue. The CFS bas been validated and is widely used to assess fatigue across multiple populations

    Measured: 30 days post-randomization

  4. Mean CFS score at 60 days post-randomization

    The CFS includes 11 likert-type questions that ask about feeling tired or lacking in energy. the questionnaire is scored from 0 to 33, with higher scores representing a higher level of fatigue. The CFS bas been validated and is widely used to assess fatigue across multiple populations

    Measured: 60 days post-randomization

  5. Mean CFS score at 90 days post-randomization

    The CFS includes 11 likert-type questions that ask about feeling tired or lacking in energy. the questionnaire is scored from 0 to 33, with higher scores representing a higher level of fatigue. The CFS bas been validated and is widely used to assess fatigue across multiple populations

    Measured: 90 days post-randomization

  6. Mean difference in change in health-related quality of life (HRQL) measured by EQ-5D-Y over 90 days from randomization

    The EQ-5D questionnaires used globally as a generic measure of health status. The EQ-5D-Y descriptive system comprises the following five dimensions: mobility, looking after myself, doing usual activities, having pain or discomfort and feeling worried, sad or unhappy. Each dimension has 3 levels: no problems, some problems and a lot of problems. The younger patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the younger patient's health state. The EQ VAS records the younger patient's self-rated health on a vertical visual analogue scale where the endpoints are labelled "The best health you can imagine" and "The worst health you can imagine".

    Measured: 90 days post-randomization

  7. Odds ratio of the all-cause death over 90 days from randomization.

    Additionally, on days 30, 60, and 90, local research personnel will ascertain participant status on the all-cause death and all-cause unplanned hospitalization endpoints

    Measured: 30, 60 and 90 days post-randomization

  8. Odds ratio of all-cause unexpected hospitalization over 90 days

    Additionally, on days 30, 60, and 90, local research personnel will ascertain participant status on the all-cause death and all-cause unplanned hospitalization endpoints

    Measured: 30, 60 and 90 days post-randomization

  9. Safety of metformin in this patient population

    Incidence of Serious Adverse Events (SAEs) and Adverse Event of Special Interest (AESIs) from the day of first visit till end of study visit (90 days post randomization)

    Measured: 90 days post-randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2023
  2. Study startApr 2024 (estimated)
  3. Primary completionOct 2024 (estimated)
  4. Study completionDec 2024 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
16 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06147050
Sponsor's protocol ID
Metformin in Long COVID
Acronym
REVIVE
Status last verified
Feb 2024
First submitted
24 Nov 2023
Last updated
4 Mar 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 34772922
  • 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.

    PubMed 33887749

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Metformin in people with Long COVID, run by Purpose Life Sciences at 1 site in Pakistan.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 4 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Zamir Hussain Suhag, MBBS, FCPS ((+92)-300-2018880, zamir.suhag@tvi.org.pk), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Pediatric Quality of Life Multidimensional Fatigue Scale (PedsQL-MFS) score at 90 days post-randomization (time frame: 90 days post-randomization). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06147050, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2024.

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