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| ID | Type | Description | Link |
|---|---|---|---|
| IISP 37693 | Other Grant/Funding Number | Merck Sharp & Dohme |
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Funding withdrawn based on unacceptably slow recruitment rate.
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Standard of Care HAART | No Intervention | Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART). | |
| Raltegravir | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Raltegravir | Drug | Oral raltegravir, 400 mg tablet, twice daily for one year. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Neurocognitive Function | 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. | Baseline, 6 months and 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Cerebrospinal Fluid | To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir. | Baseline and 12 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Bruce J Brew, MBBS, PhD | St Vincent's Hospital, Sydney | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Vincent's Hospital | Sydney | New South Wales | 2010 | Australia | ||
| The Alfred Hospital |
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Recruitment period from October 2011 to October 2013. Participants were known patients of the PI or referred from local tertiary sexual health clinics by associate investigators.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). Raltegravir : Oral raltegravir, 400 mg tablet, twice daily for one year. |
| FG001 | Standard of Care HAART | Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). Raltegravir : Oral raltegravir, 400 mg tablet, twice daily for one year. |
| BG001 | Standard of Care HAART |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Neurocognitive Function | 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. | Study was terminated prematurely with an incomplete study dataset any before any meaningful statistical analysis of the data (including change over the study time-points) could be performed. | Posted | Mean | Standard Error | Global Neurocognitive Z-Score | Baseline, 6 months and 12 months |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). Raltegravir : Oral raltegravir, 400 mg tablet, twice daily for one year. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Muscle strain | General disorders |
Early termination leading to incomplete dataset with sample size too small to produce any meaningful statistical analysis.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Bruce Brew | St. Vincent's Hospital, Sydney | 61 2 8382 1111 | 4100 | b.brew@unsw.edu.au |
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| ID | Term |
|---|---|
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
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| ID | Term |
|---|---|
| D000068898 | Raltegravir Potassium |
| ID | Term |
|---|---|
| D011760 | Pyrrolidinones |
| D011759 | Pyrrolidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Melbourne |
| Victoria |
| 3181 |
| Australia |
Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | Standard of Care HAART | Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART). |
|
|
| Secondary | Cerebrospinal Fluid | To determine if there is improvement in CSF neopterin concentrations with the addition of Raltegravir. | Study was terminated prematurely with an incomplete study dataset before any meaningful analyses of the data could be conducted. CSF was not collected at 12 months for n=1 raltegravir and n=1 control who refused lumbar puncture. | Posted | Mean | Standard Error | nmol/L | Baseline and 12 months |
|
|
|
| 0 |
| 3 |
| 1 |
| 3 |
| EG001 | Standard of Care HAART | Participants randomised to this arm will remain on their standard of care Highly Active Antiretroviral Therapy (HAART). | 0 | 3 | 1 | 3 |
| Flu-like illness | General disorders |
|
| Vitamin D deficiency | Metabolism and nutrition disorders |
|
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| D015229 |
| Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |