A Study of the Neurological Effects of Adding Raltegravir to HAART Regimen in Patients With HIV (HANDral)
A Randomised Controlled Clinical Trial of the Efficacy of HAART Intensification With Raltegravir in HIV Virally Suppressed Patients With Cognitive Impairment
HIV related cognitive impairment still occurs despite highly active antiretroviral therapy (HAART). HIV disease affects the brain in 20-40% of patients with advancing HIV disease leading to varying degrees of cognitive impairment, recently termed HIV associated neurocognitive disorders (HAND).
HAND may occur in patients who are virally suppressed in both blood and CSF. Patients with HIV Associated Neurological Disorders (HAND) who are virally suppressed in both their blood and cerebrospinal fluid (CSF), whilst on a highly active antiretroviral therapy (HAART) regimen may have significant cognitive improvement with HAART intensification with the medication Raltegravir; compared to those who remain on their existing regimen.
This study will be a prospective, interventional, randomised and unblinded controlled clinical trial. The aim of this study will be to determine whether HAART intensification with the medication Raltegravir, leads to significant improvement in HIV associated neurological disorders (HAND).
Patients with the recent progression (within 6 months) of HAND (validated by neuropsychological assessment) on HAART who are virally suppressed (<50 copies per ml) in blood and CSF will be randomised to have their existing HAART regimen intensified with raltegravir 400mg twice daily, or not. The control arm will remain on their medication regimen as prescribed. The target is to enrol 110 patients into the control group, and 110 patients into the Raltegravir intensification group.
Patients will undergo baseline neuropsychological testing, MRI, blood tests, and cerebral spinal fluid (CSF) tests (via a lumbar puncture). The methods used to determine the effectiveness of adding Raltegravir, will include further neuropsychological testing at 6 months; and neuropsychological testing, MRI and CSF assessment at 12 months. Neuropsychological testing completed at 6 and 12 months will be completed by a "blind assessor", in that they will have no knowledge of which arm (treatment or control) the participant is enrolled in.
An evaluation (neuropsychological testing) will be performed should the patient deteriorate during the course of the study, as recognised by the patient's managing physician. The decision of the Antiretroviral medication regimen to be used in such a case will be determined by the managing physician. At the end of the study protocol (12 months) the patient's HAART therapy will be managed by their primary physician.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ 4
連絡先と場所
研究場所
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New South Wales
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Sydney、New South Wales、オーストラリア、2010
- St. Vincent's Hospital
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Victoria
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Melbourne、Victoria、オーストラリア、3181
- The Alfred Hospital
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- HIV positive
- On HAART, with plasma HIV viral load < 50 copies/ml for previous 12 months or more
- Able to provide informed consent
- HAND diagnosis, with symptom progression within previous 6 months (while on existing HAART regimen)
Exclusion Criteria:
- Non-HIV related neurological disorders and active CNS opportunistic infection (as assessed by full blood count, electrolytes, creatinine, glucose, LFT's, cryptococcal antigen, VDRL, MRI brain scan and CSF fluid analysis for cell count, protein, glucose, culture, VDRL and cryptococcal antigen)
- Psychiatric disorders on the psychotic axis
- Current major depression
- Current substance use disorder, or severe substance use disorders within 12 months of study entry
- Active HCV (detectable HCV RNA)
- History of loss of consciousness > 1 hour
- Non-proficient in English
- Medications known to pharmacologically interact with ARV's
- Currently taking an Integrase Inhibitor
- Pregnancy (as assessed by the urine pregnancy test)
研究計画
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：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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介入なし：Standard of Care HAART
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART).
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実験的：Raltegravir
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART) with the addition of Raltegravir 400 mg twice daily (BID).
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Oral raltegravir, 400 mg tablet, twice daily for one year.
他の名前：
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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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Neurocognitive Function
時間枠：Baseline, 6 months and 12 months
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Change in overall neurocognitive performance, defined as a global neurocognitive z-score, over the study time-period (baseline, 6-months, 12-months).
To derive this score, 1) raw scores obtained from a 5-domain brief neurocognitive battery were converted to age-corrected z-scores (M=0, SD=1) and 2) the set of individual subtest z-scores were averaged to generate a single composite (global) z-score for each subject.
Lower (negative) scores therefore indicate greater levels of cognitive impairment.
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Baseline, 6 months and 12 months
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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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Cerebrospinal Fluid
時間枠：Baseline and 12 months
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To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir.
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Baseline and 12 months
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協力者と研究者
捜査官
- 主任研究者：Bruce J Brew, MBBS, PhD、St Vincent's Hospital, Sydney
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
キーワード
追加の関連 MeSH 用語
その他の研究ID番号
- 11/033
- IISP 37693 (その他の助成金/資金番号：Merck Sharp & Dohme)
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。
Raltegravirの臨床試験
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University of South FloridaMerck Sharp & Dohme LLC; St. Joseph's Hospital, Florida完了