Clinical trial NCT04500678: Impact of Metformin on Immuno-virologic Parameters in HIV
Official title: A 72 Week, Randomized, Open-label vs Observation Study to Assess the Potential Immuno-virologic Benefit of Metformin in HIV-infected Individuals Receiving Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: HIV/AIDS
Lead sponsor: University of Hawaii
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2020-08-05
Enrollment: 38
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Metformin vs Observation
Primary purpose: DIAGNOSTIC

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: CD4 T cell PD1+TIGIT+
timeFrame: Entry to week 72
Secondary outcomes:
measure: CD8 T cell PD1+TIGIT+
timeFrame: Entry to week 72
measure: Plasma levels of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Entry to week 72
measure: Peripheral blood CD4 T cell intracellular HIV DNA
timeFrame: Entry to week 72
measure: Peripheral blood CD4 T cell intracellular HIV RNA
timeFrame: Entry to week 72
measure: Peripheral blood monocyte intracellular HIV DNA
timeFrame: Entry to week 72
measure: Peripheral blood monocyte intracellular HIV RNA
timeFrame: Entry to week 72
Other outcomes:
measure: Safety and Tolerability: # of grade 2 or greater adverse events in each arm
timeFrame: Entry to week 72
measure: Carotid intima-media thickness
timeFrame: Entry to week 72
measure: Neuropsychological testing global Z score
timeFrame: Entry to week 72
measure: Beck's Depression Index II score
timeFrame: Entry to week 72
measure: Handgrip
timeFrame: Entry to week 72
measure: Total lean tissue by dual energy absorptiometry (DXA)
timeFrame: Entry to week 72
Locations:
city: Honolulu
country: United States
facility: John A. Burns School of Medicine, University of Hawaii - Manoa
state: Hawaii
Study officials:
affiliation: University of Hawaii
name: Cecilia M Shikuma, MD
role: PRINCIPAL_INVESTIGATOR
References: