METFORMIN HYDROCHLORIDE for HIV infection

Inclusion criteria

• {"criterion_text":"- Participant must be 50 years old or older, at the time of signing the informed consent.\n- Participants with HIV-1 infection and an uninterrupted ART regimen in the 3 months prior to study entry a. Only switch for tolerability/convenience/access reasons to generic drugs or switch from ritonavir to cobicistat would be allowed in the 3-month window and as long as the components of the regimen are unchanged.\n- HIV viral load (VL) <50 copies/mL at screening and in the year prior to study entry. a. A blip (50-200 copies/ml) would be allowed within 12 months prior to inclusion in the study, if preceded and followed by an undetectable VL determination.\n- CD4 count > 500 cel/μL at screening.\n- Participants with normal vitamin B12 levels at screening\n- Participants with normal HOMA-IR (≤ 2.6)\n- Body mass index (BMI) less than 30 Kg/m2.\n- Female participants with suspected or documented menopause a. Peri- or post-menopausal, defined as having no menstrual periods for at least 12 months prior to study entry, or skipping at least one menstrual period in the 12 months prior to study entry. Peri- or post-menopausal status will be determined for candidates who have had the uterus removed by an assessment of blood follicle stimulating hormone\n- Capable of giving signed informed consent as described in Appendix 1 which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol."}

Exclusion criteria

• {"criterion_text":"- Participants previously diagnosed with diabetes mellitus, prediabetes and body mass index > 30 kg/m2.\n- Participants with chronic hepatitis B and/or active hepatitis C or concurrent active or progressive liver disease.\n- Participants with history of any of the following comorbidities: stroke, heart failure, dementia, myocardial infarction and cancer or history of lactic acidosis.\n- Participants with decreased tissue perfusion or hemodynamic instability due to infection or other causes\n- Participants with active alcohol abuse: a. For men, heavy drinking is typically defined as consuming 15 drinks or more per week. b. For women, heavy drinking is typically defined as consuming 8 drinks or more per week.\n- Participants unable to swallow study medication tablets during the treatment period.\n- Participants receiving other medications that according to study drug label are contraindicated with metformin.\n- Participants with hypersensitivity or intolerance to any of the components of the study interventions as determined by the investigator.\n- Participants that are unwilling to abstain from participating in another interventional clinical trial during the study follow up.\n- Impaired renal function (estimated glomerular filtration rate <60 mL/min).\n- Liver laboratory abnormalities: alanine aminotransferase (ALT) over 5 times the upper limit of normal (ULN) or ALT over 3xULN and bilirubin over 1.5xULN or any verified Grade 4 laboratory abnormality that to the investigators criteria would affect the safety of the participant if included in the study.\n- Pregnant or breastfeeding women, women wishing to conceive or unwilling to commit to contraceptive methods.\n- Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant."}

Primary endpoints

• {"endpoint_text":"- EAA difference by Phenoage epigenetic clock","definition_or_measurement_approach":"Assessed by difference in epigenetic age acceleration (EAA) by PhenoAge at week 96"}

Secondary endpoints

• {"endpoint_text":"- EAA difference by Horvath´s clock, Hannum´s clock, GrimAge and PhenoAge","definition_or_measurement_approach":"EAA differences assessed by Horvath, Hannum, GrimAge and PhenoAge clocks at weeks 48, 96 and 144"}
• {"endpoint_text":"- Immune profile: % and absolute number of CD4+ T cells, CD8+ T cells, CD4+/CD8+ ratio, haematopoietic progenitors, CD4+ and CD8+ T-cell subsets (recent thymic emigrants, naïve, central and effector memory, TEMRA, activated, exhausted and senescent), T-reg, B-cell subsets (naïve, class-switched memory, non-class switched memory), NK subsets (CD56dim CD16hi, CD56hi CD16-/low) and monocytes (classic, non-classic and intermediate)","definition_or_measurement_approach":"Flow cytometry and cell counts to measure percentages and absolute numbers of listed immune cell subsets at weeks 48, 96 and 144"}
• {"endpoint_text":"- Changes in the inflammatory markers: IL-6, CRP, D-Dimer","definition_or_measurement_approach":"Laboratory measurement of IL-6, CRP and D-dimer at scheduled visits (weeks including 48, 96, 144 as per secondary objectives)"}
• {"endpoint_text":"- Changes in Telomere length in PBMC","definition_or_measurement_approach":"Telomere length measurement in PBMCs at specified timepoints (weeks 48, 96 and 144)"}
• {"endpoint_text":"- Changes in the following aging biomarkers:  TAME biomarkers: IL-6, TNFR II, hsCRP, GDF15, IGF-1, fasting insulin, cystatin C; NT-proBNP, haemoglobin A1c. Oxidative stress and DNA damage: reactive oxygen species (ROS), catalase expression, superoxide dismutase 1 - 2 levels, γH2AX histone levels. Other inflammatory and pro-coagulant biomarkers: IL-1 beta, TNF-alfa, D-dimer","definition_or_measurement_approach":"Laboratory assays for listed biomarkers and oxidative stress/DNA damage markers at scheduled timepoints (weeks 48, 96, 144)"}
• {"endpoint_text":"- Changes in the following Frailty battery: Fried frailty index, grip strength, walking speed and short physical performance battery","definition_or_measurement_approach":"Clinical assessments of frailty phenotype components and physical performance tests at weeks 48, 96 and 144"}
• {"endpoint_text":"- Changes in creatinine","definition_or_measurement_approach":"Serum creatinine laboratory measurement at scheduled visits (weeks including 24, 48, 72, 96, 120 and 144)"}
• {"endpoint_text":"- Changes in integrated and total (Gag) HIV-DNA. Changes in CA US HIV-RNA. Changes in intact proviral DNA","definition_or_measurement_approach":"Molecular assays to quantify integrated/total HIV-DNA, cell-associated unspliced HIV-RNA, and intact proviral DNA at week 48 (and as scheduled)"}

Spain

Earliest CTIS Part Ii Submission Date

05-03-2024

Latest Decision Or Authorization Date

11-03-2024

Processing Time Days

6

Number Of Sites

1

Number Of Participants

80

Primary sponsor

Full Name

Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain