Modulate Cellular Stress in the Immune Cells to Reduce Rate of Symptomatic Viral Infection

• Status: Recruiting
• Trial end date: 2023-01-01
• Target enrollment: 0
• Participant gender: All

Summary

To address Aim 1, the investigators will conduct an open-label healthy volunteer study. The study team will recruit 48 healthy adult subjects aged 21-40 years, with a Body Mass Index of 20-25 kg/m2, have no known drug allergies and are not currently receiving regular immune-modulating therapy such as metformin, NSAIDs, paracetamol, corticosteroids or statins. The age range that the investigators propose will ensure that the volunteers are likely to be healthy and not be on long-term medication for other concurrent medical conditions. Informed written consent will be obtained before any physical examination is performed. All consented subjects will undergo health screening, which includes a full physical examination, safety blood tests such as full blood count, renal, lipid and liver panel, C-Reactive Protein (CRP) test and urinary pregnancy test (for female subjects of child-bearing potential), and HbA1c to exclude diabetes mellitus. Eligible subjects will be randomized into 4 groups to receive metformin 850mg or 1000mg once or twice daily for 10 days. Aim 1 tests the hypothesis that metformin reduces ER stress in a dose-dependent manner. The primary objective of aim 1 is to define the dose and kinetics of metformin in modulating ER stress in whole blood of healthy adult volunteers.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Singapore General Hospital
• Collaborator: Duke-NUS Graduate Medical School
• Treatments: Metformin

Criteria

Inclusion Criteria:

1. Healthy adults, 21-40 years of age at time of screening

2. Body Mass Index of 20-25 kg/m2

3. No known drug allergies and are not currently receiving regular immune-modulating therapy such as metformin, NSAIDs, paracetamol, corticosteroids or statins.

4. Subjects who give written informed consent approved by the Ethical Review Board governing the site.

5. Satisfactory baseline medical assessment as assessed by physical examination and a stable health status. The laboratory values must be within the normal range of the assessing site or show abnormalities that are deemed not clinically significant as judged by the investigator. A stable health status is defined as the absence of a health event satisfying the definition of a serious adverse event.

6. Female subjects of childbearing potential may be enrolled in the study if they have negative urine pregnancy tests on the day of screening.

7. Negative for diabetes mellitus by HbA1c

8. Accessible vein at the forearm for blood collection.

9. Subjects who are willing to comply with the requirements of the study protocol and scheduled visits. (e.g., completion of the subject diary, return for follow-up visits) and who are willing to make themselves available for the duration of the study, with access to a consistent means of telephone contact, which may be either at home or at the workplace, land line, or mobile, but NOT a pay phone or other multiple-user device (i.e. a common-use phone serving multiple rooms or apartments).

Exclusion Criteria:

1. History of severe drug and/or food allergies and/or known allergies to the trial product or its components.

2. Any condition that, in the opinion of the investigator, would complicate or compromise the study or wellbeing of the subject.

3. Woman who is pregnant or breast feeding.

4. History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, neuropsychiatric, or immunosuppressive disorders that would be a risk factor when administered the Investigational Product (IP).

5. Diagnosed with cancer or on treatment for cancer within the 3 years prior to the screening.

6. Evidence of clinically significant anemia and other any significant active hematological disease, or having donated > 450 mL of blood within the past three months.

7. Evidence of substance abuse, or previous substance abuse.

8. Participation in a study involving administration of an investigational compound within the past four months, or planned participation during the duration of this study.

9. Subjects who are on long term immune-modulating therapy (e.g. NSAIDs, Paracetamol, Corticosteroids, Statins etc.) for other medical condition for the last 6 months.

10. Subject who are on long term medication for concurrent medical conditions.