Intranasal Treatment of HIV-associated Neurocognitive Disorders
2020년 6월 9일 업데이트: John Gill, University of Calgary
HAND IN Insulin-001: Intranasal Treatment of HIV-associated Neurocognitive Disorders
This study aims to see whether intranasal insulin is an effective treatment for problems with memory, concentration, slowed thinking, or any other cognitive function in people living with HIV/AIDS.
This group of signs and symptoms are called 'HIV-associated neurocognitive disorders' or HAND.
HAND can affect people living with HIV/AIDS even when they receive potent anti-HIV treatments.
Treatment of HAND by specific medication or other means is not yet available.
Intranasal insulin treatment has virtually no side-effects, and has already been tested in people with Alzheimer's disease, where it showed beneficial effects on memory, mood and quality of life
연구 개요
상세 설명
This study is designed as a prospective, double-blinded pilot study of intranasal (IN) insulin versus placebo in people with HAND (n = 20) on stable ART medication. Participants will be randomly assigned to one of two groups: 40 IU IN insulin R twice daily, or matched-volume placebo, which will be administered twice daily, taken after breakfast and again after dinner using a nasal delivery device. Serum glucose will be tested for hypoglycemia one hour after the initial administration of IN insulin or placebo and after administration at Weeks 1, 2, and 3. If the dose is tolerated and no side effects are reported the participant will continue in the study. If the dose is not tolerated due to hypoglycemia then the participant will be withdrawn from the study.
The objectives of this study are as follows:
Primary: Determine if IN insulin treatment administered twice daily for 4 months reduces overall neurocognitive deficits (based on the global z-score in people with HAND).
Secondary: Measure effects of IN insulin on individual neuropsychological domains (e.g., memory, processing speed, executive functions, motor functions) and on HAND disease progression; Define impacts of IN insulin on quality of life and mood in people with HAND; Investigate IN insulin's effects on HAND biomarker profiles in urine and blood.
연구 유형
중재적
등록 (실제)
4
단계
- 2 단계
연락처 및 위치
이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.
연구 장소
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Alberta
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Calgary, Alberta, 캐나다, T2R 0X7
- Southern Alberta Clinic
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참여기준
연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.
자격 기준
공부할 수 있는 나이
18년 이상 (성인, 고령자)
건강한 자원 봉사자를 받아들입니다
아니
연구 대상 성별
모두
설명
Inclusion Criteria:
- Documented HIV-1 infection
- Maintained on stable ART for ≥6 months (defined as undetectable viral load)
- HAND-MND or -ANI diagnosis with evidence of clinical onset or progression within the prior 2 years, based on established criteria
- Currently followed at the Southern Alberta Clinic (SAC; Calgary, AB, Canada)
Exclusion Criteria:
- HAND with a) changed dose of any medication for HIV-1 infection with a corresponding increase in viral load (e.g., ART), or b) secondary therapies for HAND (e.g., memantine, amphetamines).
- Advanced liver, renal or lung disease, cancer or diabetes requiring insulin
- Secondary diagnosis of neurocognitive impairment or other major neuropsychiatric illness such as epilepsy, Alzheimer's or Parkinson's diseases, major depression (PHQ-9 score >10), or schizophrenia
- Central nervous system lesion (diagnosed by neuroimaging) that may impair cognition
- Previous allergic reaction to insulin or any of the carrier components.
- Education < 9 years or inability to read and write English fluently
- Uncontrolled HIV-1 or hepatitis C co-infection
- Inability to perform NP or questionnaire measures, functional illiteracy
- Past or current substance abuse that could interfere with the study assessments as determined by the PI
- Marijuana use on the day of NP testing
- Uncontrolled cardiovascular disease (hypertension, coronary or peripheral artery disease)
공부 계획
이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 네 배로
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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활성 비교기: IN insulin 40 IU
Drug: IN insulin Dosage form: intranasal Dose: 40 IU Frequency: bid Duration: 16 weeks
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IN insulin twice daily taken after breakfast and again after dinner using the nasal delivery device.
다른 이름들:
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위약 비교기: IN Sterile Saline
Drug: Sterile Saline Dosage form: intranasal Frequency: bid Duration: 16 weeks
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Sterile Saline placebo twice daily taken after breakfast and again after dinner using the nasal delivery device.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Change in Global Neurocognitive Performance from Baseline
기간: 18 weeks
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Change in overall neurocognitive function as measured by the global z score.
The global z score is one measurement calculated as the average of z scores from each domain tested.
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18 weeks
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change from Baseline in Neurocognitive Performance: Memory
기간: 18 weeks
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Change from baseline in the overall z score for the memory domain, calculated as the average of z scores from: Hopkins Verbal Learning Test, Logical Memory Test, and Brief Visual Memory Test (immediate and delayed recall).
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18 weeks
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Change from Baseline in Neurocognitive Performance: Executive Function
기간: 18 weeks
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Change from baseline in the overall z score for the executive function domain, calculated as the average of z scores from: D-KEFS Trail-making Task (Letter-Switching) and Color-Word Interference (Stroop).
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18 weeks
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Change from Baseline in Neurocognitive Performance: Attention
기간: 18 weeks
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Change from baseline in the overall z score for the attention domain, calculated as the average of z scores from: Symbol Digit Modalities Test, D-KEFS Trail-making Test (Number), and Color-Word Interference (Color and Word Reading).
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18 weeks
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Change from Baseline in Neurocognitive Performance: Motor Function
기간: 18 weeks
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Change from baseline in the overall z score for the motor function domain, calculated as the average of z scores from: grooved pegboard completion times for dominant and non-dominant hands.
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18 weeks
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Change from Baseline in Neurocognitive Performance: Language
기간: 18 weeks
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Change from baseline in the overall z score for the language domain, calculated as the average of z scores from: D-KEFS Letter and Category Verbal Fluency Tasks
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18 weeks
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기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
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Change from baseline in HQoL questionnaire score
기간: 18 weeks
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Change from baseline in health-related quality of life (HQoL) questionnaire score
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18 weeks
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Change from baseline in the PHQ-9 Questionnaire score
기간: 18 weeks
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Change in the Patient Health Questionnaire-9 (PHQ-9) depressive symptoms score.
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18 weeks
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Change from Baseline in the Frailty Index Score - questionnaire and clinic assessment
기간: 16 weeks
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Change in the overall Frailty Index score measured from baseline to Week 8.
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16 weeks
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Change from Baseline HAND inflammasome biomarker laboratory result profile
기간: 16 weeks
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Change in inflammasome biomarker laboratory result profile between baseline and week 16.
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16 weeks
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Change from Baseline HAND metabolomics biomarker laboratory result profile
기간: 16 weeks
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Change in metabolomics biomarker laboratory result profile between baseline and week 16.
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16 weeks
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Change from Baseline plasma HIV-1 viral load laboratory result
기간: 16 weeks
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Change in plasma HIV-1 viral load between baseline and week 16.
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16 weeks
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Change from Baseline blood CD4 T-cell count laboratory result
기간: 16 weeks
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Change in blood CD4 T-cell count between baseline and week 16.
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16 weeks
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공동 작업자 및 조사자
여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.
협력자
수사관
- 수석 연구원: Christopher Power, MD, FRCPC, University of Alberta
- 수석 연구원: Michael J Gill, MBChB FACP, University Of Calgary
간행물 및 유용한 링크
연구에 대한 정보 입력을 담당하는 사람이 자발적으로 이러한 간행물을 제공합니다. 이것은 연구와 관련된 모든 것에 관한 것일 수 있습니다.
일반 간행물
- Claxton A, Baker LD, Hanson A, Trittschuh EH, Cholerton B, Morgan A, Callaghan M, Arbuckle M, Behl C, Craft S. Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J Alzheimers Dis. 2015;44(3):897-906. doi: 10.3233/JAD-141791. Erratum In: J Alzheimers Dis. 2015;45(4):1269-70.
- Benedict C, Hallschmid M, Hatke A, Schultes B, Fehm HL, Born J, Kern W. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004 Nov;29(10):1326-34. doi: 10.1016/j.psyneuen.2004.04.003.
- Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012 Jan;69(1):29-38. doi: 10.1001/archneurol.2011.233. Epub 2011 Sep 12.
- Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JC, DeGroodt W, Mehta P, Craft S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology. 2008 Feb 5;70(6):440-8. doi: 10.1212/01.WNL.0000265401.62434.36. Epub 2007 Oct 17. Erratum In: Neurology. 2008 Sep 9;71(11):866.
- 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.
- Power C, Boisse L, Rourke S, Gill MJ. NeuroAIDS: an evolving epidemic. Can J Neurol Sci. 2009 May;36(3):285-95. doi: 10.1017/s0317167100007009.
- 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.
- Pandya R, Krentz HB, Gill MJ, Power C. HIV-related neurological syndromes reduce health-related quality of life. Can J Neurol Sci. 2005 May;32(2):201-4. doi: 10.1017/s0317167100003978.
- Yeung H, Krentz HB, Gill MJ, Power C. Neuropsychiatric disorders in HIV infection: impact of diagnosis on economic costs of care. AIDS. 2006 Oct 24;20(16):2005-9. doi: 10.1097/01.aids.0000247565.80633.d2.
- Vivithanaporn P, Heo G, Gamble J, Krentz HB, Hoke A, Gill MJ, Power C. Neurologic disease burden in treated HIV/AIDS predicts survival: a population-based study. Neurology. 2010 Sep 28;75(13):1150-8. doi: 10.1212/WNL.0b013e3181f4d5bb. Epub 2010 Aug 25.
- Mamik MK, Asahchop EL, Chan WF, Zhu Y, Branton WG, McKenzie BA, Cohen EA, Power C. Insulin Treatment Prevents Neuroinflammation and Neuronal Injury with Restored Neurobehavioral Function in Models of HIV/AIDS Neurodegeneration. J Neurosci. 2016 Oct 12;36(41):10683-10695. doi: 10.1523/JNEUROSCI.1287-16.2016.
- Boisse L, Gill MJ, Power C. HIV infection of the central nervous system: clinical features and neuropathogenesis. Neurol Clin. 2008 Aug;26(3):799-819, x. doi: 10.1016/j.ncl.2008.04.002.
- Fujiwara, E., Gill, J.M. & Power, C. Risk Factors for HIV-Associated Neurocognitive Disorders (HAND) in a Canadian Cohort (P1.321). Neurology 86 P1.321 (2016).
- McCombe JA, Vivithanaporn P, Gill MJ, Power C. Predictors of symptomatic HIV-associated neurocognitive disorders in universal health care. HIV Med. 2013 Feb;14(2):99-107. doi: 10.1111/j.1468-1293.2012.01043.x. Epub 2012 Sep 20.
- Grant I, Franklin DR Jr, Deutsch R, Woods SP, Vaida F, Ellis RJ, Letendre SL, Marcotte TD, Atkinson JH, Collier AC, Marra CM, Clifford DB, Gelman BB, McArthur JC, Morgello S, Simpson DM, McCutchan JA, Abramson I, Gamst A, Fennema-Notestine C, Smith DM, Heaton RK; CHARTER Group. Asymptomatic HIV-associated neurocognitive impairment increases risk for symptomatic decline. Neurology. 2014 Jun 10;82(23):2055-62. doi: 10.1212/WNL.0000000000000492. Epub 2014 May 9.
- Sacktor N, Skolasky RL, Seaberg E, Munro C, Becker JT, Martin E, Ragin A, Levine A, Miller E. Prevalence of HIV-associated neurocognitive disorders in the Multicenter AIDS Cohort Study. Neurology. 2016 Jan 26;86(4):334-40. doi: 10.1212/WNL.0000000000002277. Epub 2015 Dec 30.
- Nightingale S, Winston A, Letendre S, Michael BD, McArthur JC, Khoo S, Solomon T. Controversies in HIV-associated neurocognitive disorders. Lancet Neurol. 2014 Nov;13(11):1139-1151. doi: 10.1016/S1474-4422(14)70137-1.
- Hyun E, Ramachandran R, Hollenberg MD, Vergnolle N. Mechanisms behind the anti-inflammatory actions of insulin. Crit Rev Immunol. 2011;31(4):307-40. doi: 10.1615/critrevimmunol.v31.i4.30.
- Rosenbloom MH, Barclay TR, Pyle M, Owens BL, Cagan AB, Anderson CP, Frey WH 2nd, Hanson LR. A single-dose pilot trial of intranasal rapid-acting insulin in apolipoprotein E4 carriers with mild-moderate Alzheimer's disease. CNS Drugs. 2014 Dec;28(12):1185-9. doi: 10.1007/s40263-014-0214-y.
- Claxton A, Baker LD, Wilkinson CW, Trittschuh EH, Chapman D, Watson GS, Cholerton B, Plymate SR, Arbuckle M, Craft S. Sex and ApoE genotype differences in treatment response to two doses of intranasal insulin in adults with mild cognitive impairment or Alzheimer's disease. J Alzheimers Dis. 2013;35(4):789-97. doi: 10.3233/JAD-122308.
- Shemesh E, Rudich A, Harman-Boehm I, Cukierman-Yaffe T. Effect of intranasal insulin on cognitive function: a systematic review. J Clin Endocrinol Metab. 2012 Feb;97(2):366-76. doi: 10.1210/jc.2011-1802. Epub 2011 Dec 7.
- Asahchop EL, Akinwumi SM, Branton WG, Fujiwara E, Gill MJ, Power C. Plasma microRNA profiling predicts HIV-associated neurocognitive disorder. AIDS. 2016 Aug 24;30(13):2021-31. doi: 10.1097/QAD.0000000000001160.
- Lenart N, Brough D, Denes A. Inflammasomes link vascular disease with neuroinflammation and brain disorders. J Cereb Blood Flow Metab. 2016 Oct;36(10):1668-1685. doi: 10.1177/0271678X16662043. Epub 2016 Aug 2.
- Walsh JG, Muruve DA, Power C. Inflammasomes in the CNS. Nat Rev Neurosci. 2014 Feb;15(2):84-97. doi: 10.1038/nrn3638. Epub 2014 Jan 8.
- Kim DH, Jewison DL, Milner GR, Rourke SB, Gill MJ, Power C. Neurocognitive symptoms and impairment in an HIV community clinic. Can J Neurol Sci. 2001 Aug;28(3):228-31. doi: 10.1017/s0317167100001372.
- Koenig N, Fujiwara E, Gill MJ, Power C. Montreal Cognitive Assessment Performance in HIV/AIDS: Impact of Systemic Factors. Can J Neurol Sci. 2016 Jan;43(1):157-62. doi: 10.1017/cjn.2015.306. Epub 2015 Dec 4.
- Fujiwara E, Tomlinson SE, Purdon SE, Gill MJ, Power C. Decision making under explicit risk is impaired in individuals with human immunodeficiency virus (HIV). J Clin Exp Neuropsychol. 2015;37(7):733-50. doi: 10.1080/13803395.2015.1057481. Epub 2015 Jul 24.
- Justice AC, McGinnis KA, Atkinson JH, Heaton RK, Young C, Sadek J, Madenwald T, Becker JT, Conigliaro J, Brown ST, Rimland D, Crystal S, Simberkoff M; Veterans Aging Cohort 5-Site Study Project Team. Psychiatric and neurocognitive disorders among HIV-positive and negative veterans in care: Veterans Aging Cohort Five-Site Study. AIDS. 2004 Jan 1;18 Suppl 1:S49-59.
- Crane HM, Van Rompaey SE, Dillingham PW, Herman E, Diehr P, Kitahata MM. A single-item measure of health-related quality-of-life for HIV-infected patients in routine clinical care. AIDS Patient Care STDS. 2006 Mar;20(3):161-74. doi: 10.1089/apc.2006.20.161.
- Power C, Gill MJ, Johnson RT. Progress in clinical neurosciences: The neuropathogenesis of HIV infection: host-virus interaction and the impact of therapy. Can J Neurol Sci. 2002 Feb;29(1):19-32. doi: 10.1017/s0317167100001682.
- Van Marle G, Rourke SB, Zhang K, Silva C, Ethier J, Gill MJ, Power C. HIV dementia patients exhibit reduced viral neutralization and increased envelope sequence diversity in blood and brain. AIDS. 2002 Sep 27;16(14):1905-14. doi: 10.1097/00002030-200209270-00007.
- Skinner S, Adewale AJ, DeBlock L, Gill MJ, Power C. Neurocognitive screening tools in HIV/AIDS: comparative performance among patients exposed to antiretroviral therapy. HIV Med. 2009 Apr;10(4):246-52. doi: 10.1111/j.1468-1293.2008.00679.x. Epub 2009 Jan 23.
- McCombe JA, Auer RN, Maingat FG, Houston S, Gill MJ, Power C. Neurologic immune reconstitution inflammatory syndrome in HIV/AIDS: outcome and epidemiology. Neurology. 2009 Mar 3;72(9):835-41. doi: 10.1212/01.wnl.0000343854.80344.69.
- Sacktor, N., et al. Paroxetine and Fluconazole Therapy for HAND: A Double-Blind, Placebo-Controlled Trial. Conference on retroviruses and opportunistic infections. 2016 Boston MA USA Sesssion O-12 Abstract 146(2016).
유용한 링크
연구 기록 날짜
이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.
연구 주요 날짜
연구 시작 (실제)
2018년 11월 1일
기본 완료 (실제)
2019년 4월 21일
연구 완료 (실제)
2019년 4월 21일
연구 등록 날짜
최초 제출
2017년 8월 28일
QC 기준을 충족하는 최초 제출
2017년 9월 6일
처음 게시됨 (실제)
2017년 9월 8일
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
2020년 6월 11일
QC 기준을 충족하는 마지막 업데이트 제출
2020년 6월 9일
마지막으로 확인됨
2020년 6월 1일
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
- REB17-0104
- Control# 204512 (기타 식별자: Health Canada)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
아니요
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
아니
미국 FDA 규제 기기 제품 연구
아니
미국에서 제조되어 미국에서 수출되는 제품
아니
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .
HIV 관련 신경인지 장애(HAND)에 대한 임상 시험
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St Vincent's Hospital, SydneyMerck Sharp & Dohme LLC종료됨인간 면역결핍 바이러스(HIV) | HIV 관련 신경인지 장애(HAND)호주
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Bruce BrewViiV Healthcare완전한인간 면역결핍 바이러스(HIV) | HIV 관련 신경인지 장애(HAND)호주
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University of Minnesota빼는가벼운 인지 장애(MCI) | 근위축성 측삭 경화증(ALS) | 루이소체 치매(DLB) | 알츠하이머병(AD) | 전측두엽 변성(FTLD) | 치매를 동반한 파킨슨병(PDD) | 일시적인 간질성 기억상실증(TEA) | 측두엽 간질(TLE) | 척수소뇌 운동실조증(SCA) | HIV 관련 신경인지 장애(HAND) | 원발성 측삭 경화증(PLS)미국
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