Patients with HIV and accelerated biological aging
Conditions
Interventions
Trade Name: Metformina
Product Name: Metformina
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: METFORMIN
CAS Number: 657-24-9
Concentration unit: mg milligram(s)
Concentration type: equa
Sponsors
Fundación para la Investigación Biomédica del Hospital La Paz
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Age 1. Participant must be 50 years old or older, at the time of signing the informed consent. Type of Participant and Disease Characteristics 2. 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. 3. HIV viral load (VL) 500 cel/µL at screening. 5. Participants with normal vitamin B12 levels at screening 6. Participants with normal HOMA-IR (= 2.6) Weight 7. Body mass index (BMI) less than 30 Kg/m2. Sex and Contraceptive/Barrier Requirements 8. 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 (FSH). Women with an FSH level higher than 30 mlU/mL will be eligible for the study. Informed Consent 9. 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Participants previously diagnosed with diabetes mellitus, prediabetes and body mass index > 30 kg/m2. 2. Participants with chronic hepatitis B and/or active hepatitis C or concurrent active or progressive liver disease. 3. Participants with history of any of the following comorbidities: stroke, heart failure, dementia, myocardial infarction and cancer or history of lactic acidosis. 4. Participants with decreased tissue perfusion or hemodynamic instability due to infection or other causes 5. 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. 6. Participants unable to swallow study medication tablets during the treatment period. Prior/Concomitant Therapy 7. Participants receiving other medications that according to study drug label are contraindicated with metformin. 8. Participants with hypersensitivity or intolerance to any of the components of the study interventions as determined by the investigator. Prior/Concurrent Clinical Study Experience 9. Participants that are unwilling to abstain from participating in another interventional clinical trial during the study follow up. Diagnostic assessments 10. Impaired renal function (estimated glomerular filtration rate <60 mL/min). 11. 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. Other Exclusions 12. Pregnant or breastfeeding women, women wishing to conceive or unwilling to commit to contraceptive methods. 13. Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the anti-aging affect of metformin compared to placebo as assessed by difference in epigenetic age acceleration (EAA) by Phenoage at week 96;Secondary Objective: • To evaluate the anti-ageing effect of metformin compared to placebo as assessed by difference in EAA by four epigenetic clocks at week 48, 96 and 144 • To evaluate the effect of metformin compared to placebo as assessed by the immune profile recovery at week 48, 96 and 144 • To evaluate the effect of metformin compared to placebo as assessed by the inflammatory biomarkers’ changes at week 48, 96 and 144 • To evaluate the effect of metformin compared to placebo as assessed by the leucocyte telomere length changes at week 48, 96 and 144 • To evaluate the effect of metformin compared to placebo as assessed by the different aging biomarkers changes at week 48, 96 and 144 • To evaluate the effect of metformin compared to placebo as assessed by the frailty phenotype improvement at week 48, 96 and 144 • To evaluate the security of metformin compared to placebo as assessed by lab parameters at week 24, 48, 72, 96, 120 and 144;Primary end point(s): EAA difference by Phenoage epigenetic clock;Timepoint(s) of evaluation of this end point: 96 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • EAA difference by Horvath´s clock, Hannum´s clock, GrimAge and PhenoAge • 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) • Changes in the inflammatory markers: IL-6, CRP, D-Dimer • Changes in Telomere length in PBMC 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, ?H2AX histone levels. • Other inflammatory and pro-coagulant biomarkers: IL-1 beta, TNF-alfa, D-dimer • Changes in the following Frailty battery: Fried frailty index, grip strength, walking speed and short physical performance battery • Changes in creatinine;Timepoint(s) of evaluation of this end point: - Weeks 48, 96 and 144 - Weeks 48, 96 and 144 - Weeks 48, 96 and 144 - Weeks 48, 96 and 144 - Weeks 48, 96 and 144 - Weeks 48, 96 and 144 - Weeks 24, 48, 72, 96, 120 and 144 | — |
Countries
Spain
Contacts
Public ContactRocío María
Fundación para la Investigación Biomédica del Hospital La Paz
Outcome results
None listed