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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04500678
Other study ID # H046
Secondary ID
Status Recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date February 1, 2019
Est. completion date December 31, 2022

Study information

Verified date August 2020
Source University of Hawaii
Contact Cecilia M Shikuma, MD
Phone 808 692-1328
Email shikuma@hawaii.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Non-diabetic, aviremic HIV-infected individuals on antiretroviral therapy (ART) will be randomized to metformin therapy or to observation for 72 weeks. Primary objective is to assess change over 72 weeks in CD4 T cell negative checkpoint receptors (PD-1 and TIGIT). As secondary objectives the study will look at 72 week change in other immuno-virologic parameters (CD8 T cell negative checkpoint receptors, plasma indoleamine 2,3-dioxygenase (IDO) levels and CD4 T cell and monocyte intracellular HIV DNA and HIV RNA. The study will also explore the 72 week impact of metformin on change in carotid intima-media thickness (cIMT) as a surrogate marker of atherosclerosis, on neuropsychological (NP) performance, strength, and change in body composition.


Recruitment information / eligibility

Status Recruiting
Enrollment 38
Est. completion date December 31, 2022
Est. primary completion date February 1, 2022
Accepts healthy volunteers No
Gender All
Age group 40 Years and older
Eligibility Inclusion Criteria:

- HIV+

- On suppressive ART stable for > 1 year

- Plasma HIV RNA < 50 copies/mL within 3 months of entry, with no HIV RNA > 200 copies/mL within the past 6 months prior to entry

- Age >40 years

- Ability and willingness to provide written informed consent

Exclusion Criteria:

- Uncontrolled chronic medical condition or cancer

- Acute illness within 2 weeks of entry

- Diagnosis of diabetes by history, fasting blood glucose >126, or by HgbA1c > 6.5

- Chronic, uncontrolled diarrhea

- Known hypersensitivity or contraindication to metformin use

- Current presence of hepatitis C including currently on or intent to start therapy for hepatitis C within the 48 week duration of study.

- Serum B12 level below the reference normal range as listed by the commercial lab utilized for this study (Diagnostic Laboratory Services)

- Pregnancy, or intent to become pregnant or nursing an infant

- Any immunomodulator, HIV vaccine, any other vaccine, or investigational therapy within 30 days of study entry.

- Current uncontrolled coronary artery disease or NYHA Class 3 or 4 congestive heart failure

- History of liver cirrhosis

- Current use of zidovudine, stavudine or didanosine

- The following lab values

- Hemoglobin < 9.0 g/dL

- Absolute neutrophil count < 1000/µL

- Platelet count < 50,000/µL

- AST (SGOT) and ALT (SGPT) > 5x upper limit of normal (ULN)

- Calculated creatinine clearance (Cockcroft and Gault) < 50 ml/min

- Active or recent past history (within past 2 years) of illicit substance or alcohol use or abuse which, in the judgment of the Investigator, will interfere with the patient's ability to comply with the protocol requirements

- Patients, who, in the opinion of the Investigator, are unable to comply with the dosing schedule and protocol evaluation or for whom the study may not be advisable

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Metformin
Metformin 500 mg Extended Release (ER) qd increasing to 1000 mg ER qd at week 4 and continued to week 48.

Locations

Country Name City State
United States John A. Burns School of Medicine, University of Hawaii - Manoa Honolulu Hawaii

Sponsors (2)

Lead Sponsor Collaborator
University of Hawaii Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Other Safety and Tolerability: # of grade 2 or greater adverse events in each arm Comparison of the # of grade 2 or greater adverse events in the 2 arms Entry to week 72
Other Carotid intima-media thickness Comparison of change over time in the thickness of the right carotid intima-media thickness (mm) as assessed by carotid ultrasound in the 2 study arms Entry to week 72
Other Neuropsychological testing global Z score Comparison of change over time in the age, gender and education-adjusted neuropsychological testing global Z score in the 2 study arms [The z score has a mean of zero and a standard deviation of 1; higher than 0 is better cognitive performance and lower than 0 is lower performance than the mean] Entry to week 72
Other Beck's Depression Index II score Comparison of change over time in the Beck's Depression Index II score in the 2 study arms [21-item rating scale with maximum score of 63; higher scores are indicative of worse depression] Entry to week 72
Other Handgrip Comparison of change over time in handgrip strength (kg) as assessed by a handgrip dynamometer in the 2 study arms Entry to week 72
Other Total lean tissue by dual energy absorptiometry (DXA) Comparison of change over time in total lean tissue (kg) as assessed by DXA in the 2 study arms Entry to week 72
Primary CD4 T cell PD1+TIGIT+ Comparison of change over time in percentage of CD4 T cells bearing the PD1+TIGIT+ surface markers in peripheral blood mononuclear cells (PBMC) in the treatment (metformin) arm compared to the observation arm Entry to week 72
Secondary CD8 T cell PD1+TIGIT+ Comparison of change over time in percentage of CD8 T cells bearing the PD1+TIGIT+ surface markers in PBMCs in the 2 study arms Entry to week 72
Secondary Plasma levels of indoleamine 2,3-dioxygenase (IDO) Comparison of change over time in the levels of IDO [assessed as a ratio of L-kynurenine (kyn) to substrate tryptophan (trp)] in mass spectrometry assays Entry to week 72
Secondary Peripheral blood CD4 T cell intracellular HIV DNA Comparison of change over time in the number of intracellular HIV DNA copies per million CD4 T cells in PBMC in the 2 study arms Entry to week 72
Secondary Peripheral blood CD4 T cell intracellular HIV RNA Comparison of change over time in the number of intracellular HIV RNA copies per million CD4 T cells in PBMC in the 2 study arms Entry to week 72
Secondary Peripheral blood monocyte intracellular HIV DNA Comparison of change over time in the number of intracellular HIV DNA copies per million monocytes in PBMC in the 2 study arms Entry to week 72
Secondary Peripheral blood monocyte intracellular HIV RNA Comparison of change over time in the number of intracellular HIV RNA copies per million monocytes in PBMC in the 2 study arms Entry to week 72
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