Clinical trial NCT02663934: Exercise Training to Improve Brain Health in Older HIV+ Individuals
Official title: Exercise Training to Improve Brain Health in Older HIV+ Individuals
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: HIV
Keywords: HIV, AIDS, Cognition, Memory, Exercise, Stretching
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: University of Missouri, St. Louis
name: University of California, San Diego
First posted: 2016-01-26
Enrollment: 75
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Management and treatment of older persons living with HIV (PLWH) (≥ 40 years old) is becoming increasingly more complex as a majority is greater than 40 years old. This proposal will conduct a prospective controlled intervention trial to assess the quantitative and qualitative effects of a monitored aerobic/resistance exercise (EXS) program compared to a social-interaction stretching (SIS) program on brain health (neuropsychological performance testing and neuroimaging measurements) in older PLWH. These results could influence public health policy by encouraging PLWH to adopt a more physically active lifestyle and stimulate the development of effective EXS programs for older PLWH.

Detailed description: Management of older persons living with HIV (PLWH) (≥ 40 years old) is becoming increasingly more complex as a majority is greater than 40 years old. Attempts to improve the quality of life of older PLWH using adjunctive therapeutics to combination antiretroviral therapy (cART) have largely been unsuccessful.

While the impact of physical activity on brain health (assessed by neuropsychological performance and neuroimaging) has been well studied in older healthy HIV uninfected (HIV-) individuals and neurodegenerative conditions, few studies have concentrated on older PLWH. Both clinically and pathophysiologically, HIV associated neurocognitive disorders (HAND) differs from other neurodegenerative disorders seen with aging (e.g. Alzheimer's disease (AD). A positive association relationship between exercise and cognition has been observed in PLWH, but physical activity has been primarily examined using self-report questionnaires that are subjective and not quantitative. To date, no study has focused on the direct effects of exercise on neuropsychological performance or neuroimaging in PLWH.

The objective of this proposal is to conduct a prospective controlled intervention trial to determine if an increase in physical activity through a monitored aerobic and resistance exercise (EXS) program improves brain health in older PLWH. We will quantify physical function (physical activity using cardiorespiratory capacity and actigraphy) and brain function \[neuropsychological performance testing and neuroimaging (cerebral blood flow (CBF) and brain volume)\] in older physically inactive PLWH at baseline and 26 weeks after randomization to either an EXS or a social-interaction stretching (SIS) program. In addition, we will obtain stool samples, serum markers of neurogenesis, glucose regulation, and systemic inflammation.

A direct impact of these expected outcomes will be the adoption of a more physically active lifestyle by older PLWH and improved EXS guidelines and programs for older PLWH.

Eligibility criteria: Inclusion Criteria:

1. age \> 40 years old
2. documented history of HIV infection
3. on stable combination antiretroviral therapy (cART) for approximately 3 months with undetectable plasma HIV RNA
4. physically inactive-sedentary lifestyle (approximately \<2 hours of exercise/week) and not engaged in regular exercise for approximately 3 months prior to enrollment
5. approximately 9 years of education
6. able to have an MRI
7. able to provide written informed consent (does not have LAR, POA, etc.)

Exclusion Criteria:

1. approximately \>2x/week of moderate (or greater) exercise
2. cardiovascular/cerebrovascular disease or pulmonary disease that precludes ability to safely exercise
3. significant neurological disorders (e.g. stroke, head injury with loss of consciousness for \>30 minutes, developmental learning disability
4. presence of dementia or behavioral disorders that would prevent ability to follow the protocol
5. alcohol or substance abuse/ dependence within the last 6 months (DSM-4 TR)
6. contraindications to MRI scanning (e.g. claustrophobia, pacemaker)
7. pregnant or breast-feeding
8. unable to provide written informed consent

Primary outcomes:
measure: Change in Global Cognition From Baseline to Follow up, in Exercise Group vs. Stretching Group
timeFrame: 6 months
measure: Changes in Brain Structural/Functional Measures in Older PLWH
timeFrame: 26 weeks
measure: Change in Level of Daily Activity
timeFrame: 6 Months
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Beau M Ances, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Spudich S. HIV and neurocognitive dysfunction. Curr HIV/AIDS Rep. 2013 Sep;10(3):235-43. doi: 10.1007/s11904-013-0171-y.
citation: Spudich S, Gonzalez-Scarano F. HIV-1-related central nervous system disease: current issues in pathogenesis, diagnosis, and treatment. Cold Spring Harb Perspect Med. 2012 Jun;2(6):a007120. doi: 10.1101/cshperspect.a007120.
citation: Clifford DB, Ances BM. HIV-associated neurocognitive disorder. Lancet Infect Dis. 2013 Nov;13(11):976-86. doi: 10.1016/S1473-3099(13)70269-X.
citation: Shah S, Mildvan D. HIV and aging. Curr Infect Dis Rep. 2006 May;8(3):241-7. doi: 10.1007/s11908-006-0065-x.
citation: Valcour V, Paul R. HIV infection and dementia in older adults. Clin Infect Dis. 2006 May 15;42(10):1449-54. doi: 10.1086/503565. Epub 2006 Apr 13.
citation: Hall HI, Song R, Rhodes P, Prejean J, An Q, Lee LM, Karon J, Brookmeyer R, Kaplan EH, McKenna MT, Janssen RS; HIV Incidence Surveillance Group. Estimation of HIV incidence in the United States. JAMA. 2008 Aug 6;300(5):520-9. doi: 10.1001/jama.300.5.520.
citation: Ortega M, Ances BM. Role of HIV in amyloid metabolism. J Neuroimmune Pharmacol. 2014 Sep;9(4):483-91. doi: 10.1007/s11481-014-9546-0. Epub 2014 May 10.
citation: Xu J, Ikezu T. The comorbidity of HIV-associated neurocognitive disorders and Alzheimer's disease: a foreseeable medical challenge in post-HAART era. J Neuroimmune Pharmacol. 2009 Jun;4(2):200-12. doi: 10.1007/s11481-008-9136-0. Epub 2008 Nov 19.
citation: Cohen RA, Seider TR, Navia B. HIV effects on age-associated neurocognitive dysfunction: premature cognitive aging or neurodegenerative disease? Alzheimers Res Ther. 2015 Apr 6;7(1):37. doi: 10.1186/s13195-015-0123-4. eCollection 2015.
citation: Desquilbet L, Jacobson LP, Fried LP, Phair JP, Jamieson BD, Holloway M, Margolick JB. A frailty-related phenotype before HAART initiation as an independent risk factor for AIDS or death after HAART among HIV-infected men. J Gerontol A Biol Sci Med Sci. 2011 Sep;66(9):1030-8. doi: 10.1093/gerona/glr097. Epub 2011 Jun 30.
citation: Justice AC. HIV and aging: time for a new paradigm. Curr HIV/AIDS Rep. 2010 May;7(2):69-76. doi: 10.1007/s11904-010-0041-9.
citation: Justice AC, McGinnis KA, Skanderson M, Chang CC, Gibert CL, Goetz MB, Rimland D, Rodriguez-Barradas MC, Oursler KK, Brown ST, Braithwaite RS, May M, Covinsky KE, Roberts MS, Fultz SL, Bryant KJ; VACS Project Team. Towards a combined prognostic index for survival in HIV infection: the role of 'non-HIV' biomarkers. HIV Med. 2010 Feb;11(2):143-51. doi: 10.1111/j.1468-1293.2009.00757.x. Epub 2009 Sep 14.
citation: Onen NF, Agbebi A, Shacham E, Stamm KE, Onen AR, Overton ET. Frailty among HIV-infected persons in an urban outpatient care setting. J Infect. 2009 Nov;59(5):346-52. doi: 10.1016/j.jinf.2009.08.008. Epub 2009 Aug 23.
citation: Casau NC. Perspective on HIV infection and aging: emerging research on the horizon. Clin Infect Dis. 2005 Sep 15;41(6):855-63. doi: 10.1086/432797. Epub 2005 Jul 28.
citation: Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12.
citation: Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. J Alzheimers Dis. 2010;22(2):569-79. doi: 10.3233/JAD-2010-100768.
citation: Damirchi A, Tehrani BS, Alamdari KA, Babaei P. Influence of aerobic training and detraining on serum BDNF, insulin resistance, and metabolic risk factors in middle-aged men diagnosed with metabolic syndrome. Clin J Sport Med. 2014 Nov;24(6):513-8. doi: 10.1097/JSM.0000000000000082.
citation: Balsamo S, Willardson JM, Frederico Sde S, Prestes J, Balsamo DC, Dahan da CN, Dos Santos-Neto L, Nobrega OT. Effectiveness of exercise on cognitive impairment and Alzheimer's disease. Int J Gen Med. 2013 May 24;6:387-91. doi: 10.2147/IJGM.S35315. Print 2013.
citation: Rao AK, Chou A, Bursley B, Smulofsky J, Jezequel J. Systematic review of the effects of exercise on activities of daily living in people with Alzheimer's disease. Am J Occup Ther. 2014 Jan-Feb;68(1):50-6. doi: 10.5014/ajot.2014.009035.
citation: Walker JM, Klakotskaia D, Ajit D, Weisman GA, Wood WG, Sun GY, Serfozo P, Simonyi A, Schachtman TR. Beneficial effects of dietary EGCG and voluntary exercise on behavior in an Alzheimer's disease mouse model. J Alzheimers Dis. 2015;44(2):561-72. doi: 10.3233/JAD-140981.
citation: Dufour CA, Marquine MJ, Fazeli PL, Henry BL, Ellis RJ, Grant I, Moore DJ; HNRP Group. Physical exercise is associated with less neurocognitive impairment among HIV-infected adults. J Neurovirol. 2013 Oct;19(5):410-7. doi: 10.1007/s13365-013-0184-8. Epub 2013 Aug 10.
citation: Fazeli PL, Woods SP, Heaton RK, Umlauf A, Gouaux B, Rosario D, Moore RC, Grant I, Moore DJ; HNRP Group. An active lifestyle is associated with better neurocognitive functioning in adults living with HIV infection. J Neurovirol. 2014 Jun;20(3):233-42. doi: 10.1007/s13365-014-0240-z. Epub 2014 Feb 20.
citation: Fillipas S, Oldmeadow LB, Bailey MJ, Cherry CL. A six-month, supervised, aerobic and resistance exercise program improves self-efficacy in people with human immunodeficiency virus: a randomised controlled trial. Aust J Physiother. 2006;52(3):185-90. doi: 10.1016/s0004-9514(06)70027-7.
citation: Mapstone M, Hilton TN, Yang H, Guido JJ, Luque AE, Hall WJ, Dewhurst S, Shah K. Poor Aerobic Fitness May Contribute to Cognitive Decline in HIV-infected Older Adults. Aging Dis. 2013 Aug 27;4(6):311-9. doi: 10.14336/AD.2013.0400311. eCollection 2013.
citation: Mattson MP. Exercise and the brain: a slap on the HAND. J Neurovirol. 2013 Oct;19(5):407-9. doi: 10.1007/s13365-013-0208-4. Epub 2013 Sep 27. No abstract available.
citation: Rodrigues AM, O'Brien N, French DP, Glidewell L, Sniehotta FF. The question-behavior effect: genuine effect or spurious phenomenon? A systematic review of randomized controlled trials with meta-analyses. Health Psychol. 2015 Jan;34(1):61-78. doi: 10.1037/hea0000104. Epub 2014 Aug 18.
citation: Gill AJ, Kolson DL. Chronic inflammation and the role for cofactors (hepatitis C, drug abuse, antiretroviral drug toxicity, aging) in HAND persistence. Curr HIV/AIDS Rep. 2014 Sep;11(3):325-35. doi: 10.1007/s11904-014-0210-3.
citation: Rosenfield PL. The potential of transdisciplinary research for sustaining and extending linkages between the health and social sciences. Soc Sci Med. 1992 Dec;35(11):1343-57. doi: 10.1016/0277-9536(92)90038-r.
citation: Thorpe KE, Zwarenstein M, Oxman AD, Treweek S, Furberg CD, Altman DG, Tunis S, Bergel E, Harvey I, Magid DJ, Chalkidou K. A pragmatic-explanatory continuum indicator summary (PRECIS): a tool to help trial designers. CMAJ. 2009 May 12;180(10):E47-57. doi: 10.1503/cmaj.090523. Epub 2009 Apr 16. No abstract available.
citation: Masters MC, Ances BM. Role of neuroimaging in HIV-associated neurocognitive disorders. Semin Neurol. 2014 Feb;34(1):89-102. doi: 10.1055/s-0034-1372346. Epub 2014 Apr 8.