Intranasal Treatment of HIV-associated Neurocognitive Disorders
2020年6月9日 更新者：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
調査の概要
詳細な説明
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 If the dose is not tolerated due to hypoglycemia then the participant will be withdrawn from the study.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.
研究の種類
介入
入学 (実際)
4
段階
- フェーズ2
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究場所
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Alberta
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Calgary、Alberta、カナダ、T2R 0X7
- Southern Alberta Clinic
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
18年歳以上 (大人、高齢者)
健康ボランティアの受け入れ
いいえ
受講資格のある性別
全て
説明
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)
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：ランダム化
- 介入モデル：並列代入
- マスキング：4倍
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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アクティブコンパレータ：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.
他の名前：
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プラセボコンパレーター：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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change in Global Neurocognitive Performance from Baseline
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change from Baseline in Neurocognitive Performance: Memory
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Change from baseline in HQoL questionnaire score
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
協力者
捜査官
- 主任研究者：Christopher Power, MD, FRCPC、University of Alberta
- 主任研究者：Michael J Gill, MBChB FACP、University of Calgary
出版物と役立つリンク
研究に関する情報を入力する責任者は、自発的にこれらの出版物を提供します。これらは、研究に関連するあらゆるものに関するものである可能性があります。
一般刊行物
- 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).
便利なリンク
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (実際)
2018年11月1日
一次修了 (実際)
2019年4月21日
研究の完了 (実際)
2019年4月21日
試験登録日
最初に提出
2017年8月28日
QC基準を満たした最初の提出物
2017年9月6日
最初の投稿 (実際)
2017年9月8日
学習記録の更新
投稿された最後の更新 (実際)
2020年6月11日
QC基準を満たした最後の更新が送信されました
2020年6月9日
最終確認日
2020年6月1日
詳しくは
本研究に関する用語
その他の研究ID番号
- REB17-0104
- Control# 204512 (その他の識別子：Health Canada)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
いいえ
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
米国で製造され、米国から輸出された製品。
いいえ
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
HIV関連神経認知障害（HAND）の臨床試験
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St Vincent's Hospital, SydneyMerck Sharp & Dohme LLC終了しましたヒト免疫不全ウイルス (HIV) | HIV関連神経認知障害（HAND）オーストラリア
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Bruce BrewViiV Healthcare完了ヒト免疫不全ウイルス (HIV) | HIV関連神経認知障害（HAND）オーストラリア
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University of Minnesota引きこもった軽度認知障害 (MCI) | 筋萎縮性側索硬化症（ALS） | レビー小体型認知症（DLB） | アルツハイマー病 (AD) | 前頭側頭葉変性症 (FTLD) | 認知症を伴うパーキンソン病（PDD） | 一過性てんかん性健忘症（TEA） | 側頭葉てんかん（TLE） | 脊髄小脳失調症 (SCA) | HIV関連神経認知障害（HAND） | 原発性側索硬化症 (PLS)アメリカ
IN insulinの臨床試験
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HK inno.N Corporation積極的、募集していない
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HK inno.N Corporationまだ募集していません軽度から中等度のアトピー性皮膚炎
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HK inno.N Corporationまだ募集していません
-
BlueWillow BiologicsPorton Biopharma Ltd.完了