Overview
Sponsor-declared trial summary
Phase
Phase I and Phase II (Integrated) - Bioequivalence study
Status
Ongoing, recruitment ended
Participants planned
80
Countries
1
Sites
1
HIV infection
To evaluate the anti-aging effect of metformin compared to placebo as assessed by difference in epigenetic age acceleration (EAA) by Phenoage at week 96
Key facts
- Sponsor
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz, Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Virus Diseases [C02]
- Trial duration
- 3 Dec 2021 → ongoing
- Decision date (initial)
- 2024-03-11
- Transition trial
- Yes
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
External identifiers
- EU CT number
- 2024-512287-54-00
- EudraCT number
- 2021-003299-15
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Others, Safety
To evaluate the anti-aging effect of metformin compared to placebo as assessed by difference in epigenetic age acceleration (EAA) by Phenoage at week 96
Secondary objectives 8
- To evaluate the anti-aging 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 increase in immune profile recovery at week 48, 96 and 144
- To evaluate the effect of metformin compared to placebo as assessed by the reduction of 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
- To evaluate the effect of metformin compared to placebo as assessed by the viral reservoir parameters´ changes at week 48
Conditions and MedDRA coding
HIV infection
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | A double blinded, phase II, placebo controlled, single center randomized clinical trial. Randomized, placebo-controlled, double-blind superiority design.
|
Randomised Controlled | Double | [{"id":47708,"code":1,"name":"Subject"},{"id":47709,"code":2,"name":"Investigator"}] | Metformin placebo: Route of administration: oral. Metformin (Metformin 850 mg film-coated tablet): Route of administration: oral. Dose: Metformin 850 mg/day. Dosage: one 850 mg film coated-tablet once daily during the first 4 weeks followed by one 850 mg film coated-tablet twice daily 92 weeks, except in persons receiving dolutegravir who would maintain the 850 mg dose once daily due to the pharmacological interaction Intervention: starting Metformin 850mg treatment. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 9
- Participant must be 50 years old or older, at the time of signing the informed consent.
- 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.
- 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.
- CD4 count > 500 cel/μL at screening.
- Participants with normal vitamin B12 levels at screening
- Participants with normal HOMA-IR (≤ 2.6)
- Body mass index (BMI) less than 30 Kg/m2.
- 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
- 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 13
- Participants previously diagnosed with diabetes mellitus, prediabetes and body mass index > 30 kg/m2.
- Participants with chronic hepatitis B and/or active hepatitis C or concurrent active or progressive liver disease.
- Participants with history of any of the following comorbidities: stroke, heart failure, dementia, myocardial infarction and cancer or history of lactic acidosis.
- Participants with decreased tissue perfusion or hemodynamic instability due to infection or other causes
- 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.
- Participants unable to swallow study medication tablets during the treatment period.
- Participants receiving other medications that according to study drug label are contraindicated with metformin.
- Participants with hypersensitivity or intolerance to any of the components of the study interventions as determined by the investigator.
- Participants that are unwilling to abstain from participating in another interventional clinical trial during the study follow up.
- Impaired renal function (estimated glomerular filtration rate <60 mL/min).
- 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.
- Pregnant or breastfeeding women, women wishing to conceive or unwilling to commit to contraceptive methods.
- Any comorbidities or treatment with experimental drugs that according to the investigator could bias study results or entail additional risks for the participant.
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- EAA difference by Phenoage epigenetic clock
Secondary endpoints 8
- 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, γH2AX 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
- Changes in integrated and total (Gag) HIV-DNA. Changes in CA US HIV-RNA. Changes in intact proviral DNA
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Metformina Pensa Pharma 850 mg comprimidos recubiertos con película EFG
PRD544883 · Product
- Active substance
- Metformin Hydrochloride
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Authorisation status
- Authorised
- ATC code
- A10BA02 — METFORMIN
- Marketing authorisation
- 71.119
- MA holder
- TOWA PHARMACEUTICAL S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Sponsor organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Address
- Paseo De La Castellana 261
- City
- Madrid
- Postcode
- 28046
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Contact name
- Jose Ramon Arribas Lopez
Public contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Contact name
- Jose Ramon Arribas Lopez
Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Sponsor organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Address
- Paseo De La Castellana 261
- City
- Madrid
- Postcode
- 28046
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Contact name
- Jose Ramon Arribas Lopez
Public contact point
- Organisation
- Fundacion Para La Investigacion Biomedica Del Hospital Universitario La Paz
- Contact name
- Jose Ramon Arribas Lopez
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruitment ended | 80 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2021-12-03 | 2022-03-02 | 2022-11-03 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-03-05 | Spain | Acceptable 2024-03-11
|
2024-03-11 |