COMO: Cognition Study With HIV+ Patients (CTNPT 015) (COMO)
Primary Purpose
HIV - Human Immunodeficiency Virus, Cognitive Symptoms
Status
Terminated
Phase
Early Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Change in antiretrovirals
Sponsored by
About this trial
This is an interventional treatment trial for HIV - Human Immunodeficiency Virus focused on measuring Human Immunodeficiency Virus, HIV, Cognitive symptoms, Cognitive evaluation, Neuropsychological testing, Quality of life, Anxiety, Viral load, Antiretroviral, Cerebrospinal fluid, Lumbar puncture, Magnetic resonance imaging, MRI
Eligibility Criteria
Inclusion Criteria:
- are 18 years and older
- have the capacity to give informed consent as determined by the research nurse
- have unexplained cognitive decline (reported either by the patient or an outside informant)
- have been on a stable ART regimen for > 6 months
- have an undetectable viral load in plasma for at least 6 months (a single blip of ≤ 150 copies/mL will be accepted)
- have not had a change in medications that could potentially interfere with cognition in the past 4 months
Exclusion Criteria:
- detectable VL in the plasma
- past history of dementia
- past history of Central Nervous System opportunistic infection or stroke
- current substance abuse ( as per DSM-IV criteria) other than cigarettes
- coagulopathy
- thrombocytopenia
- use of Coumadin
- intra-cranial hypertension
Sites / Locations
- Montreal Chest Institute - Chronic Viral Illness Service - McGill University Health Centre (MUHC)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Change in ARVs to improve cognition
Arm Description
Change in ARVs to improve cognition: Personalized change in antiretrovirals will be based on CSF analysis
Outcomes
Primary Outcome Measures
Changes in neurocognitive functioning over 6 months
Cognition will be assessed at study entry and 6 months with the following tests: Letter Fluency, Category Fluency, Letter-Number Sequencing, Digit-Symbol, Symbol Search, Grooved Pegboard, Hopkins Verbal Learning Test-Revised, Stroop, Brief Visuospatial Memory Test-Revised, Tower of London, Trail Making Test A and B, Spatial Span, Montreal Cognitive Assessment (MoCA), and a brief computerized battery of tests (B-CAM).
Secondary Outcome Measures
Full Information
NCT ID
NCT02144688
First Posted
March 29, 2014
Last Updated
March 15, 2016
Sponsor
Marie-Josée Brouillette
Collaborators
Fonds de la Recherche en Santé du Québec, CIHR Canadian HIV Trials Network
1. Study Identification
Unique Protocol Identification Number
NCT02144688
Brief Title
COMO: Cognition Study With HIV+ Patients (CTNPT 015)
Acronym
COMO
Official Title
CTNPT 015 - Pilot Project to Implement a Step-wise Investigation That Includes Cerebrospinal (CSF) Analysis as a Standard of Care for HIV+ Individuals With Cognitive Symptoms
Study Type
Interventional
2. Study Status
Record Verification Date
March 2016
Overall Recruitment Status
Terminated
Why Stopped
In 14 participants who had LP, very low level viremia was found in only 1
Study Start Date
June 2011 (undefined)
Primary Completion Date
March 2016 (Actual)
Study Completion Date
March 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Marie-Josée Brouillette
Collaborators
Fonds de la Recherche en Santé du Québec, CIHR Canadian HIV Trials Network
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to contribute evidence towards the potential to improve cognition in HIV+ individuals experiencing cognitive decline through personalized change in antiretroviral (ARV) medication. To that end, following a comprehensive evaluation to identify confounding clinical conditions, study participants will undergo a lumbar puncture to: (i) measure viral load (at 2 copies/ml); (ii) identify Cerebrospinal Fluid (CSF) genotype and tropism; and (iii) measure concentration of antiretroviral agents. When indicated from the CSF analysis, a personalized change in ARV will be implemented. Cognition will be measured in all at study entry and 6 months later.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV - Human Immunodeficiency Virus, Cognitive Symptoms
Keywords
Human Immunodeficiency Virus, HIV, Cognitive symptoms, Cognitive evaluation, Neuropsychological testing, Quality of life, Anxiety, Viral load, Antiretroviral, Cerebrospinal fluid, Lumbar puncture, Magnetic resonance imaging, MRI
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Change in ARVs to improve cognition
Arm Type
Experimental
Arm Description
Change in ARVs to improve cognition: Personalized change in antiretrovirals will be based on CSF analysis
Intervention Type
Drug
Intervention Name(s)
Change in antiretrovirals
Intervention Description
Change in ARVs to improve cognition: Personalized change in antiretrovirals will be based on CSF analysis
Primary Outcome Measure Information:
Title
Changes in neurocognitive functioning over 6 months
Description
Cognition will be assessed at study entry and 6 months with the following tests: Letter Fluency, Category Fluency, Letter-Number Sequencing, Digit-Symbol, Symbol Search, Grooved Pegboard, Hopkins Verbal Learning Test-Revised, Stroop, Brief Visuospatial Memory Test-Revised, Tower of London, Trail Making Test A and B, Spatial Span, Montreal Cognitive Assessment (MoCA), and a brief computerized battery of tests (B-CAM).
Time Frame
6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
are 18 years and older
have the capacity to give informed consent as determined by the research nurse
have unexplained cognitive decline (reported either by the patient or an outside informant)
have been on a stable ART regimen for > 6 months
have an undetectable viral load in plasma for at least 6 months (a single blip of ≤ 150 copies/mL will be accepted)
have not had a change in medications that could potentially interfere with cognition in the past 4 months
Exclusion Criteria:
detectable VL in the plasma
past history of dementia
past history of Central Nervous System opportunistic infection or stroke
current substance abuse ( as per DSM-IV criteria) other than cigarettes
coagulopathy
thrombocytopenia
use of Coumadin
intra-cranial hypertension
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marie-Josée Brouillette, MD, FRCPC
Organizational Affiliation
Montreal Chest Institute - Chronic Viral Illness Service - McGill University Health Centre (MUHC)
Official's Role
Principal Investigator
Facility Information:
Facility Name
Montreal Chest Institute - Chronic Viral Illness Service - McGill University Health Centre (MUHC)
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2X 2P4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
17914061
Citation
Antinori A, Arendt G, Becker JT, Brew BJ, Byrd DA, Cherner M, Clifford DB, Cinque P, Epstein LG, Goodkin K, Gisslen M, Grant I, Heaton RK, Joseph J, Marder K, Marra CM, McArthur JC, Nunn M, Price RW, Pulliam L, Robertson KR, Sacktor N, Valcour V, Wojna VE. Updated research nosology for HIV-associated neurocognitive disorders. Neurology. 2007 Oct 30;69(18):1789-99. doi: 10.1212/01.WNL.0000287431.88658.8b. Epub 2007 Oct 3.
Results Reference
background
PubMed Identifier
123519
Citation
Morrison NE, Collins FM. Immunogenicity of an aerogenic BCG vaccine in T-cell-depleted and normal mice. Infect Immun. 1975 May;11(5):1110-21. doi: 10.1128/iai.11.5.1110-1121.1975.
Results Reference
background
PubMed Identifier
15075493
Citation
Becker JT, Lopez OL, Dew MA, Aizenstein HJ. Prevalence of cognitive disorders differs as a function of age in HIV virus infection. AIDS. 2004 Jan 1;18 Suppl 1:S11-8.
Results Reference
background
PubMed Identifier
20100092
Citation
Canestri A, Lescure FX, Jaureguiberry S, Moulignier A, Amiel C, Marcelin AG, Peytavin G, Tubiana R, Pialoux G, Katlama C. Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin Infect Dis. 2010 Mar 1;50(5):773-8. doi: 10.1086/650538.
Results Reference
background
PubMed Identifier
15512922
Citation
Carey CL, Woods SP, Gonzalez R, Conover E, Marcotte TD, Grant I, Heaton RK; HNRC Group. Predictive validity of global deficit scores in detecting neuropsychological impairment in HIV infection. J Clin Exp Neuropsychol. 2004 May;26(3):307-19. doi: 10.1080/13803390490510031.
Results Reference
background
PubMed Identifier
15075495
Citation
Cherner M, Ellis RJ, Lazzaretto D, Young C, Mindt MR, Atkinson JH, Grant I, Heaton RK; HIV Neurobehavioral Research Center Group. Effects of HIV-1 infection and aging on neurobehavioral functioning: preliminary findings. AIDS. 2004 Jan 1;18 Suppl 1:S27-34.
Results Reference
background
PubMed Identifier
19474412
Citation
Cysique LA, Vaida F, Letendre S, Gibson S, Cherner M, Woods SP, McCutchan JA, Heaton RK, Ellis RJ. Dynamics of cognitive change in impaired HIV-positive patients initiating antiretroviral therapy. Neurology. 2009 Aug 4;73(5):342-8. doi: 10.1212/WNL.0b013e3181ab2b3b. Epub 2009 May 27.
Results Reference
background
PubMed Identifier
19424802
Citation
Cysique LA, Brew BJ. Neuropsychological functioning and antiretroviral treatment in HIV/AIDS: a review. Neuropsychol Rev. 2009 Jun;19(2):169-85. doi: 10.1007/s11065-009-9092-3. Epub 2009 May 9.
Results Reference
background
PubMed Identifier
16682686
Citation
Cysique LA, Maruff P, Brew BJ. Variable benefit in neuropsychological function in HIV-infected HAART-treated patients. Neurology. 2006 May 9;66(9):1447-50. doi: 10.1212/01.wnl.0000210477.63851.d3.
Results Reference
background
PubMed Identifier
12177366
Citation
De Luca A, Ciancio BC, Larussa D, Murri R, Cingolani A, Rizzo MG, Giancola ML, Ammassari A, Ortona L. Correlates of independent HIV-1 replication in the CNS and of its control by antiretrovirals. Neurology. 2002 Aug 13;59(3):342-7. doi: 10.1212/wnl.59.3.342.
Results Reference
background
PubMed Identifier
12056927
Citation
Ellis RJ, Moore DJ, Childers ME, Letendre S, McCutchan JA, Wolfson T, Spector SA, Hsia K, Heaton RK, Grant I. Progression to neuropsychological impairment in human immunodeficiency virus infection predicted by elevated cerebrospinal fluid levels of human immunodeficiency virus RNA. Arch Neurol. 2002 Jun;59(6):923-8. doi: 10.1001/archneur.59.6.923.
Results Reference
background
PubMed Identifier
18852864
Citation
Florkowski CM. Sensitivity, specificity, receiver-operating characteristic (ROC) curves and likelihood ratios: communicating the performance of diagnostic tests. Clin Biochem Rev. 2008 Aug;29 Suppl 1(Suppl 1):S83-7.
Results Reference
background
PubMed Identifier
19247836
Citation
Hardy DJ, Vance DE. The neuropsychology of HIV/AIDS in older adults. Neuropsychol Rev. 2009 Jun;19(2):263-72. doi: 10.1007/s11065-009-9087-0. Epub 2009 Feb 27.
Results Reference
background
PubMed Identifier
17502721
Citation
McCutchan JA, Wu JW, Robertson K, Koletar SL, Ellis RJ, Cohn S, Taylor M, Woods S, Heaton R, Currier J, Williams PL. HIV suppression by HAART preserves cognitive function in advanced, immune-reconstituted AIDS patients. AIDS. 2007 May 31;21(9):1109-17. doi: 10.1097/QAD.0b013e3280ef6acd.
Results Reference
background
PubMed Identifier
10883716
Citation
Jones RN, Gallo JJ. Dimensions of the Mini-Mental State Examination among community dwelling older adults. Psychol Med. 2000 May;30(3):605-18. doi: 10.1017/s0033291799001853.
Results Reference
background
PubMed Identifier
19307324
Citation
Koski L, Xie H, Finch L. Measuring cognition in a geriatric outpatient clinic: Rasch analysis of the Montreal Cognitive Assessment. J Geriatr Psychiatry Neurol. 2009 Sep;22(3):151-60. doi: 10.1177/0891988709332944. Epub 2009 Mar 23.
Results Reference
background
PubMed Identifier
18195140
Citation
Letendre S, Marquie-Beck J, Capparelli E, Best B, Clifford D, Collier AC, Gelman BB, McArthur JC, McCutchan JA, Morgello S, Simpson D, Grant I, Ellis RJ; CHARTER Group. Validation of the CNS Penetration-Effectiveness rank for quantifying antiretroviral penetration into the central nervous system. Arch Neurol. 2008 Jan;65(1):65-70. doi: 10.1001/archneurol.2007.31.
Results Reference
background
PubMed Identifier
15349869
Citation
Letendre SL, McCutchan JA, Childers ME, Woods SP, Lazzaretto D, Heaton RK, Grant I, Ellis RJ; HNRC Group. Enhancing antiretroviral therapy for human immunodeficiency virus cognitive disorders. Ann Neurol. 2004 Sep;56(3):416-23. doi: 10.1002/ana.20198.
Results Reference
background
PubMed Identifier
12707454
Citation
Marra CM, Lockhart D, Zunt JR, Perrin M, Coombs RW, Collier AC. Changes in CSF and plasma HIV-1 RNA and cognition after starting potent antiretroviral therapy. Neurology. 2003 Apr 22;60(8):1388-90. doi: 10.1212/01.wnl.0000058768.73358.1a.
Results Reference
background
PubMed Identifier
19424052
Citation
Marra CM, Zhao Y, Clifford DB, Letendre S, Evans S, Henry K, Ellis RJ, Rodriguez B, Coombs RW, Schifitto G, McArthur JC, Robertson K; AIDS Clinical Trials Group 736 Study Team. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNA and neurocognitive performance. AIDS. 2009 Jul 17;23(11):1359-66. doi: 10.1097/QAD.0b013e32832c4152.
Results Reference
background
PubMed Identifier
16914973
Citation
Nath A, Sacktor N. Influence of highly active antiretroviral therapy on persistence of HIV in the central nervous system. Curr Opin Neurol. 2006 Aug;19(4):358-61. doi: 10.1097/01.wco.0000236614.51592.ca.
Results Reference
background
PubMed Identifier
1733335
Citation
Nilsson C, Stahlberg F, Thomsen C, Henriksen O, Herning M, Owman C. Circadian variation in human cerebrospinal fluid production measured by magnetic resonance imaging. Am J Physiol. 1992 Jan;262(1 Pt 2):R20-4. doi: 10.1152/ajpregu.1992.262.1.R20.
Results Reference
background
PubMed Identifier
11399956
Citation
Pilcher CD, Shugars DC, Fiscus SA, Miller WC, Menezes P, Giner J, Dean B, Robertson K, Hart CE, Lennox JL, Eron JJ Jr, Hicks CB. HIV in body fluids during primary HIV infection: implications for pathogenesis, treatment and public health. AIDS. 2001 May 4;15(7):837-45. doi: 10.1097/00002030-200105040-00004.
Results Reference
background
PubMed Identifier
10509569
Citation
Price RW, Yiannoutsos CT, Clifford DB, Zaborski L, Tselis A, Sidtis JJ, Cohen B, Hall CD, Erice A, Henry K. Neurological outcomes in late HIV infection: adverse impact of neurological impairment on survival and protective effect of antiviral therapy. AIDS Clinical Trial Group and Neurological AIDS Research Consortium study team. AIDS. 1999 Sep 10;13(13):1677-85. doi: 10.1097/00002030-199909100-00011.
Results Reference
background
PubMed Identifier
17721099
Citation
Robertson KR, Smurzynski M, Parsons TD, Wu K, Bosch RJ, Wu J, McArthur JC, Collier AC, Evans SR, Ellis RJ. The prevalence and incidence of neurocognitive impairment in the HAART era. AIDS. 2007 Sep 12;21(14):1915-21. doi: 10.1097/QAD.0b013e32828e4e27.
Results Reference
background
PubMed Identifier
15097298
Citation
Robertson KR, Robertson WT, Ford S, Watson D, Fiscus S, Harp AG, Hall CD. Highly active antiretroviral therapy improves neurocognitive functioning. J Acquir Immune Defic Syndr. 2004 May 1;36(1):562-6. doi: 10.1097/00126334-200405010-00003.
Results Reference
background
PubMed Identifier
17292021
Citation
Schultz-Larsen K, Kreiner S, Lomholt RK. Mini-Mental Status Examination: mixed Rasch model item analysis derived two different cognitive dimensions of the MMSE. J Clin Epidemiol. 2007 Mar;60(3):268-79. doi: 10.1016/j.jclinepi.2006.06.007. Epub 2006 Aug 10.
Results Reference
background
PubMed Identifier
15365130
Citation
Valcour V, Shikuma C, Shiramizu B, Watters M, Poff P, Selnes O, Holck P, Grove J, Sacktor N. Higher frequency of dementia in older HIV-1 individuals: the Hawaii Aging with HIV-1 Cohort. Neurology. 2004 Sep 14;63(5):822-7. doi: 10.1212/01.wnl.0000134665.58343.8d.
Results Reference
background
PubMed Identifier
16619159
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.
Results Reference
background
PubMed Identifier
18580585
Citation
Wouters H, van Gool WA, Schmand B, Lindeboom R. Revising the ADAS-cog for a more accurate assessment of cognitive impairment. Alzheimer Dis Assoc Disord. 2008 Jul-Sep;22(3):236-44. doi: 10.1097/WAD.0b013e318174f8b9.
Results Reference
background
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COMO: Cognition Study With HIV+ Patients (CTNPT 015)
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