Cognition Metabolism and Exercise Among Women Living With HIV in Puerto Rico (CMEx)

Soluble Insulin Receptor Dysfunction Correlates With HAND in HIV+ Women on CART

The study evaluates the association between soluble insulin receptor dysfunction, cardiorespiratory fitness, and HIV associated neurocognitive disorder (HAND). Those who volunteer to participate in the study will have two evaluations at study entry that include a dual x-ray absorptiometry (DEXA) densitometry, anthropometry, neurocognitive testing, blood and urine samples for metabolic testing, and a cardiorespiratory fitness testing. DEXA will be conducted in the Endocrinology Unit at the University Hospital, Medical Center (letter of support included). The cardiorespiratory fitness testing will be conducted in the AIDS Clinical Trials Unit (ACTU) project, University of Puerto Rico, Medical Sciences Campus, and the Puerto Rico Clinical and Translational Research Consortium. Then, participants will be invited to participate in a 6-week, 3 days/week individualized exercise program. The exercise program will be conducted at the University of Puerto Rico Medical Sciences Campus. After completion of the exercise program, study entry evaluations will be repeated. The duration of the study will take approximately 10 weeks.

Study Overview

• Status: Unknown
• Conditions: HIV
• Intervention / Treatment: Other: High intensity interval training (HIIT)

Detailed Description

The aim of the study is to determine the effect of a low volume high intensity interval training (HIIT) exercise intervention on cardio-respiratory fitness (CR-fitness), insulin resistance, and cognitive function among normally active but physically untrained HIV+ Hispanic women. The primary hypotheses are that HIIT will improve: 1) CR-fitness in all groups (HIV+ and HIV-), 2) insulin sensitivity in both groups of HIV+ women, and 3) cognitive function as determined by hippocampal function in HIV+ women with HAND. Participants will receive 2 weeks, 6 sessions of 8 x 60 seconds cycling bouts eliciting approximately 80% of maximal heart rate with 60 second rest between bouts after which they will receive 4 week, 12 sessions of 10 x 60 seconds cycling bouts eliciting approximately 90% of maximal heart rate with 60 second rest between bouts. Then, participants will be evaluated with a CR-fitness, insulin resistance, anthropometry, and neurocognitive function tests.

Participants will undergo an intervention (described above) designed for normally active but physically untrained HIV+ Hispanic women, one with (n=15) and other without (n=15) neurocognitive impairment & HIV- controls (n=15). After the HIIT intervention, measurements of CR-fitness, insulin resistance, and cognitive function including hippocampal function using the memory island test will be obtained, as well as CR-fitness, anthropometry, DEXA densitometry, and blood and urine samples for metabolic testing. The ultimate goal is to improve the understanding of mechanisms by which exercise influence neurocognitive function; thus, providing a potential non-pharmacological alternative to prevent, control or reduce chronic incapacitating diseases in HIV+ Hispanic adults.

• Study Type: Interventional
• Enrollment (Anticipated): 45
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Farah A. Ramirez-Marrero, PhD; Phone Number: 787-602-0088; Email: farah.ramirez1@upr.edu
• Study Contact Backup: Name: Valerie Wojna-Muniz, MD; Phone Number: 2819 787-758-2525; Email: valerie.wojna1@upr.edu

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00936
    • Recruiting
    • Medical Sciences Campus
    • Contact: Farah A. Ramirez-Marrero, PhD; Phone Number: 787-602-0088; Email: farah.ramirez1@upr.edu
    • Contact: Valerie Wojna-Muniz, MD; Phone Number: 2819 787-758-252; Email: valerie.wojna1@upr.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. HIV-seropositive women ≥21 years with lymphocytes differentiated cells 4 (CD4) cell count or nadir in the last year ≤500 cells/mm3, or viral load ≥1,000 copies/mL despite highly active antiretroviral therapy (HAART).
2. Education level ≥9th grade, since is the minimum required for some of the neuro-psychological (NP) tests. All HIV-seropositive and HIV-seronegative participants will be tested for vocabulary and reading pre-morbid cognitive function as described below.
3. Non-drug abusers; defined as those with <5 exposures in a lifetime to drugs (opiates/heroin, methamphetamine, cocaine/crack, speed ball). For the purpose of this study neither tobacco nor nicotine use will be considered a drug.
4. No diagnosis of diabetes or the use of hypoglycemic agents.

Exclusion Criteria:

1. HIV+ women and men <21 years old with CD4 cell count >500 cells/mm3 and/or viral load <1,000 copies/mL.
2. Opportunistic infections of the central nervous system (CNS) as determined by neurological evaluation and neuroimaging. (Neuroimaging studies, if needed, will be performed as part of patient care and hence have not been included as a budget item in this proposal.)
3. History of diabetes or the use hypoglycemic agents.
4. Underlying neurologic and/or neuropsychiatric disorders such as cerebrovascular events; history of meningitis/encephalitis, CNS opportunistic infections, or seizures; head trauma (<6 months with loss of consciousness for >1 hr); cerebral palsy; or any other neuropsychiatric condition that in the judgment of the investigators may affect the study.
5. Active systemic infection or illness, which in the judgment of the investigators may affect the study.
6. Pregnant/nursing mothers or women with recent birth (<60 days).
7. Substance abuse: active drug use - all participants will be screened with urine toxicology and active alcohol abuse - those scoring >3 points in the Michigan Alcoholism Screening Test (MAST) will be screened with blood samples for alcohol levels (Seltzer 1975).
8. Patients who are unwilling to give informed consent or incapable of understanding informed consent.

9. Education less than 9th grade.

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Study Plan

How is the study designed?

Design Details

• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hispanic women living with HIV; High intensity interval training (HIIT) on normally active but physically untrained HIV+ Hispanic women, one with (n=15) and other without (n=15) neuro-cognitive impairment (HAND) on antiretroviral therapy (CART) receive 2 weeks, 6 sessions of 8 x 60 seconds cycling bouts eliciting approximately 80% of maximal heart rate with 60 second rest between bouts after which they will receive 4 week, 12 sessions of 10 x 60 seconds cycling bouts eliciting approximately 90% of maximal heart rate with 60 second rest between bouts.	Other: High intensity interval training (HIIT); Six weeks, three days per week (total of 18 sessions) of HIIT cycle ergometer exercise protocol
Experimental: Hispanic women living without HIV; High intensity interval training (HIIT) on a comparison group of 15 Hispanic women without HIV receive 2 weeks, 6 sessions of 8 x 60 seconds cycling bouts eliciting approximately 80% of maximal heart rate with 60 second rest between bouts after which they will receive 4 week, 12 sessions of 10 x 60 seconds cycling bouts eliciting approximately 90% of maximal heart rate with 60 second rest between bouts.	Other: High intensity interval training (HIIT); Six weeks, three days per week (total of 18 sessions) of HIIT cycle ergometer exercise protocol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardio-respiratory fitness as measured by maximal oxygen consumption (VO2max)	Maximal oxygen consumption	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolic syndrome classification based on the National Cholesterol Education Program (NCEP) criteria	Number of participants with abnormal values in 3 or more of the following: fasting glucose, resting blood pressure, waist circumference, fasting triglycerides, and HDL.	6 weeks
Neurocognitive function as measured by memory testing	Number of participants with abnormal values of neurocognitive function will be identified. Measures of memory testing using questionnaires and a computer-based assessment will be aggregated to arrive at one reported value of neurocognitive function.	6 weeks

Collaborators and Investigators

• Sponsor: University of Puerto Rico
• Investigators: Principal Investigator: Farah A. Ramirez-Marrero, PhD, University of Puerto Rico

Publications and helpful links

General Publications

• Ramirez-Marrero FA, Perez-Frontera S, Amalbert-Birriel MA, Matos M, Santana-Bagur J, Frontera WR, Wojna V. Brief Report: Effects of Low-Volume High-Intensity Interval Training in Hispanic HIV+ Women: A Nonrandomized Study. J Acquir Immune Defic Syndr. 2020 Jul 1;84(3):285-289. doi: 10.1097/QAI.0000000000002353.

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: October 5, 2016
• First Submitted That Met QC Criteria: November 9, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Estimate): November 11, 2016
• Last Update Submitted That Met QC Criteria: November 9, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Exercise; Metabolism; Neurocognition; Hispanic women
• Other Study ID Numbers: UPuertoRico

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED