Mitochondria in HIV and Aging (MITO+)

NCT03489421 | Completed

• 1 other identifier: 17-2161
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Older adults with human immunodeficiency virus (HIV) and a long history of antiretroviral therapy have more mitochondrial dysfunction- the cells that help them make energy. This dysfunction in mitochondria may lead to symptoms of muscle fatigue, physical function impairment, and impaired exercise tolerance compared to HIV-uninfected controls of a similar age and body mass index (BMI). Furthermore, the investigators hypothesize that the older antiretroviral therapy (ART) of tenofovir disoproxil fumarate (TDF) is associated with greater impairment in mitochondrial function than the newer agent, tenofovir alafenamide (TAF).

Conditions

Human Immunodeficiency Virus (HIV); Mitochondrial Diseases

Outcome Measures

Primary Outcomes (1)

• ADP/ATP measurement (mitochondrial function)

  ADP/ATP ratio between HIV-infected and uninfected subjects

  At Baseline

Secondary Outcomes (5)

• Protein citrate synthase

  At Baseline

• Respiratory control ratio (RCR)

  At Baseline

• Inflammatory markers

  At Baseline

• Muscle function

  At Baseline

• TDF to TAF change

  At Baseline

Study Arms (2)

HIV Infected

Un-infected controls

Controls without HIV from a historical pre-approved-IRB-protocol database

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

HIV-infected participants will be those living with HIV, between the ages of 50-75 years, recruited from the University of Colorado Infectious Diseases Group Practice HIV-uninfected participants were previous enrolled and completed an IRB approved protocol (historical database).

You may qualify if:

• Between the ages of 50-75 years at study entry (a subset of participants changing from TDF-based ART to TAF-based ART will also have mitochondrial function measured and the age range for this subset is 18-70)
• Known HIV infection or presumed HIV uninfected (will be confirmed at screening)
• For HIV+ participants: must be on an ART regimen (change in regimen permitted for preference/tolerability but not for virologic failure) for a minimum of 5 years, with a viral load \< 200 during the prior 2 years. The investigators will initially target 10 years of therapy, but will expand to 5 years if needed for enrollment.
• Although any ART regimen will be allowed if effective (as above), the investigators will first target participants that have a history of \> 5 years of TDF exposure and are currently on TAF or TDF, but no prior exposure to AZT or stavudine.
• CD4 T-cell count greater than 200 cells/mm3
• All participants must be able to perform activities of daily living without assistance, and ambulate independently.
• Sedentary as defined above
• Post-menopausal as defined by cessation of menstrual periods for at least 12 months without any other obvious pathological or physiological cause OR removal of ovaries at least 12 months prior to enrollment.
• Body mass index between 25-38 kg/m2

You may not qualify if:

• Participation in another clinical trial where the therapy is unknown or blinded.
• Diabetes, as defined by use of diabetes medications, hemoglobin A1c 6.5 or greater, fasting plasma glucose 126 mg/dL or greater, or random plasma glucose 200 mg/dL or greater.
• Persons on statin therapy (as possible; this criteria may be removed for recruitment difficulties).
• Fasting triglycerides \> 400
• Untreated or incompletely treated thyroid disease will be excluded; stable therapy for \> 6 months will be allowed.
• Persons on growth hormone or growth hormone axis therapy (i.e., tesamorelin) will be excluded.
• The investigators will initially target men, women, or transgendered individuals without replacement hormone use. If the investigators are unable to recruit the target number of participants, stable (\>3 months) estrogen or testosterone within physiologic replacement dose range will be permitted.
• Corticosteroid use, including intra-articular, will be excluded (within 3 months for oral; within 6 months for intra-articular); inhaled or intranasal will be permitted.
• Immunosuppressive medications within 6 months, including methotrexate, infliximab, azathioprine, etc.
• Women that are pregnant, breast-feeding, or intend to become pregnant.
• Known hepatitis B or C with detectable viremia within in the past 6 months.
• Hepatitis C with undetectable viral load for at least 6 months will be allowed.
• Known mitochondrial disorder
• Severe liver disease other than hepatitis B or C due to interference with systemic cytokine production
• Uncontrolled hypertension defined as resting systolic blood pressure (BP) \>180 mmHg or diastolic BP \>100 mmHg

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado - Anschutz Medical Campus

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Mitochondrial Diseases

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 25, 2018
• First Posted: April 5, 2018
• Study Start: December 15, 2018
• Primary Completion: September 5, 2019
• Study Completion: September 5, 2019
• Last Updated: September 26, 2019

Record last verified: 2019-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)