HIV InfectionsPhase 2NCT00361257
Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults
A Phase 2 study testing Minocycline in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 16 sites in United States.
Trial summary
The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Minocycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 16 sitesUnited States
- Study dates
- Mar 2007to Jan 2010
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infected
- Currently on a stable ART regimen for at least 16 consecutive weeks prior to study entry. Participants whose regimens have changed with respect to dose or formulation are eligible, but patients who have changed to different drugs in the same class are not eligible. Participants taking atazanavir must also be taking ritonavir or a ritonavir-boosted drug to be eligible for this study. More information on this criterion can be found in the protocol.
- Plan to stay on current ART regimen between study screening and Week 24
- AIDS Dementia Scale (ADC) Stage greater than 0
- Cognitive impairment, as evidenced by neuropsychological tests administered at screening
- Progressive neurocognitive decline. More information on this criterion can be found in the protocol.
Show all 11Show fewer
- Estimated premorbid IQ of 70 or higher indicated by an age-corrected scaled score of 5 or higher on the vocabulary section of the Wechsler Adult Intelligence Scale Revised (WAIS-R) administered at study screening
- Karnofsky performance score of 60 or higher
- Ability to sit and stand for at least 2 hours and swallow medications with an 8-ounce glass of water
- Willing to use acceptable methods of contraception
- Willing to adhere to study schedule
Who cannot join
- Current cancers. Patients with basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or cancer not requiring systemic chemotherapy are not excluded.
- Severe premorbid psychiatric illness, including schizophrenia and major depression, which, in the opinion of the investigator, may interfere with the study
- Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
- Previous or current confounding neurological disorders. More information on this criterion can be found in the protocol.
- Central nervous system infections or cancers. More information on this criterion can be found in the protocol.
- Systemic lupus
Show all 18Show fewer
- Thyroid disease diagnosed within 24 weeks of study entry
- Active drug or alcohol abuse that, in the opinion of the investigator, may interfere with the study
- Serious illness requiring systemic treatment or hospitalization. Patients who complete therapy or are clinically stable on therapy are not excluded.
- Investigational agents within 45 days prior to study entry. Patients taking expanded access drugs or drugs used in an ACTG protocol for HIV treatment or for HIV-associated complications that are not prohibited by this protocol are not excluded.
- History of allergy/sensitivity to minocycline or other tetracyclines and their formulations
- Any esophageal or other condition that would interfere with a patient's ability to swallow study medication
- Participation in a previous clinical drug research trial of HIV-associated cognitive impairment. Patients who have had an objective decline in performance as defined by the protocol are not excluded.
- Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the study
- Certain medications
- Certain abnormal laboratory values. Patients who test positive on nonreactive rapid plasma reagin tests (RPR)are not excluded.
- Inability to undergo lumbar punctures
- Breastfeeding
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
United States16 sites
The Ponce de Leon Ctr. CRS
Atlanta, Georgia, 30308
Johns Hopkins School of Medicine
Baltimore, Maryland, 21287-8106
Massachusetts General Hospital, Division of Infectious Diseases
Boston, Massachusetts, 02114
University of North Carolina, AIDS Clinical Trials Unit
Chapel Hill, North Carolina, 27514
Northwestern University CRS
Chicago, Illinois, 60611
University of Colorado Health Science Center
Denver, Colorado, 80262-3706
Henry Ford Hosp. CRS
Detroit, Michigan, 48202
UCLA-David Geffen School of Medicine
Los Angeles, California, 90035
NYU Med Ctr, Dept of Medicine
New York, New York, 10016
University of Pennsylvania, ACTU
Philadelphia, Pennsylvania, 19104
The Research and Education Group - Portland CRS
Portland, Oregon, 97209
Virginia Commonwealth Univ. Medical Ctr. CRS
Richmond, Virginia, 23219
1101 University of Rochester Medical Center, Division of Infectious Diseases
Rochester, New York, 14642
University of California
San Diego, California, 92103
Univ of Washington, Harborview Medical Ctr
Seattle, Washington, 98104
Washington University
St Louis, Missouri, 63108-2138
About this study
Official title: Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment
The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.
Read the detailed description
Cognitive impairment, including disabling cognitive, behavioral, and social dysfunction, continues to be a major problem faced by HIV-infected people taking antiretroviral therapy (ART). Research is needed to develop treatment that can be given alongside ART to prevent or lessen cognitive impairment caused by ART. Minocycline, an antibiotic commonly used for the treatment of acne and rheumatoid arthritis, has demonstrated anti-inflammatory and neuroprotective properties in previous studies. This study will evaluate the effectiveness of 24-week therapy with minocycline in lessening the cognitive impairment of HIV infected adults taking ART.
This study will last at least 24 weeks and has two steps. Patients will be stratified by HIV viral load and their neurocognitive state at study screening. In Step I, patients will be randomly assigned to one of two groups. Group 1 participants will receive twice-daily minocycline for 24 weeks; Group 2 participants will receive placebo. At the end of Phase I, study participants will be offered to enter Step II; all participants in Step II will receive twice-daily minocycline for an additional 24 weeks.
There will be a total of 8 study visits: 5 visits for Step I (including the entry visit) and 3 visits for Step II. Medical history will occur at all visits. Blood collection will occur at all visits. Participants who have positive nonreactive rapid plasma regain (RPR) values at screening will have mandatory lumbar punctures; for those with negative serum RPR results lumbar punctures are optional. Participants who test positive for syphilis will also have a lumbar puncture at their discretion to determine if syphilis has affected the brain. A neurological exam, other neuropsychological, dementia, and depression scale assessments, and urine collection will occur at most visits. Patients will be asked to complete a questionnaire on daily living at study entry and Weeks 12 and 24. Patients who have a lumbar puncture at Week 24 will receive a phone call 2 to 5 days after the procedure to report any adverse effects. Some participants may also have an electrocardiogram (ECG) during the study. For participants not on atazanavir some procedures and sample collections are optional.
- Conditions
- HIV Infections
- Being tested
- Minocycline, Placebo (Tetracycline)
- Keywords
- Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MinocyclineDrug
Tetracycline antibiotic, 100 mg taken orally every 12 hours
Placebo (Tetracycline)Drug
Tetracycline antibiotic placebo, orally every 12 hours
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Minocycline | Experimental | 100 mg orally every 12 hours Receives: Drug: Minocycline |
| Arm 2: Matching placebo | Placebo comparator | orally every 12 hours Receives: Drug: Placebo (Tetracycline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cognitive Performance Compared to Baseline
Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are:
- Grooved Pegboard Dominant Hand (GPD)
- Grooved Pegboard Non-dominant hand (GPN)
- Choice Reaction Time (CRT)
- Sequential Reaction Time (QRT)
- Timed Gait (TIG)
- Trail Making Part A (TMA)
- Trail Making Part B (TMB)
- Symbol Digit (SYD) The primary outcome is NPZ-8 score at week24 - NPZ-8 score at baseline.
Measured: At baseline and week 24
Secondary outcomes (23)
Change in Global Deficit Z-Score (GDS)
GDS on the test battery is the simple average of all 14 individual deficit scores in the test battery, including Time Gait, Grooved Pegboard Test for the dominant and non-dominant hands, Trail Making Test parts A and B, Symbol Digit Test, simple and sequential reaction time - CalCAP, Hopkins Verbal Learning Test (Revised)- Learning, Delayed Recall and Recognition trials, and Stroop Color Interference Test-color, word, and interference tasks. The outcome is the 24 week change of GDS Z-score (24 week-baseline).
Measured: At baseline and week 24
Change in Investigator's Clinical Global Impression Score (ICGIS)
Clinicians were asked to rate their overall impression about the clinical improvement or worsening of his/her study participants. They can choose from the following 7 levels: (0) No Change, (1) Mild Improvement, (2) Moderate Improvement, (3) Marked Improvement, (4) Mild Worsening, (5) Moderate Worsening, and (6) Marked Worsening.
For the analysis, we simplified the outcome into the following 3 levels: (0) worsened, (1) No Change, and (2) Improved.
Measured: At week 24
Change in Cognitive Gross Motor Function Domain Z-Score
The cognitive gross motor function is a age and education adjusted z score of Timed Gait (TIG). The outcome is the 24 week change of cognitive gross motor function domain z-scores (week 24-baseline).
Measured: At baseline and week 24
Change in Fine Motor Function Domain Z-Score
The fine motor function domain score is an average of age, sex, education, and African-American ethnicity adjusted z scores of Grooved Pegboard Dominant Hand (GPD) and Grooved Pegboard Non-dominant hand (GPN). The outcome is a 24 week change of the fine motor function domain z-score (week 24-baseline).
Measured: At baseline and week 24
Change in Psychomotor Function Domain Z-Score
The psychomotor function domain score us the average of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA) and Trail Making Part B (TMB). The outcome is the 24 week change of psychomotor function domain z-scores (week24-baseline).
Measured: At baseline and week 24
Change in Fine Motor/Nonverbal Function Domain Z-Score
The fine motor/nonverbal function domain score is a age and education adjusted z score of Symbol Digit Test (SYD) The outcome is the 24 change of fine motor/nonverbal function domain z-score (week 24-baseline).
Measured: At baseline and week 24
Change in Information Processing Function Domain Z-Score
The information processing function domain score is the average of age and education adjusted z scores of simple and sequential reaction time - CalCAP. The outcome is the 24 week change of information processing function domain z-scores (week 24-baseline).
Measured: At baseline and week 24
Change in Verbal Memory Domain Z-Score
The verbal memory domain score is the average of age and education adjusted z scores of Hopkins Verbal Learning Test- Revised, Learning and Delayed Recall. The outcome is the 24 week change of verbal memory domain z-scores (week 24-baseline).
Measured: At baseline and week 24
Change in Frontal Systems Function Domain Z-Score
The frontal systems function domain score is the average of age and education adjusted z scores of Stroop Color Interference Test (CTP) and interference task (STP). The outcome is the 24 week change of frontal systems function domain z-score (week 24-baseline).
Measured: At baseline and week 24
Change in Karnofsky Performance Score
The original Karnofsky performance score is 11 level score which ranges between 0 to 100. The score 100 means normal and 0 means death; therefore, higher score means higher ability to perform daily tasks.
For the analysis, a new dichotomous variable (no change/worse vs. better at 24 weeks compared to baseline) was created.
Measured: At baseline and week 24
Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks)
The outcome was the 24 week change in CD4 cell count (week 24-baseline).
Measured: At baseline and weeks 24
Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks)
The outcome was the 24 week change of CD8 cell counts (week 24-baseline).
Measured: At baseline and week 24
Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
Grade or higher means that adverse events were moderate, severe, or life-threatening, or death. Grade 2 or higher adverse events are lised in the Adverse Event section.
Measured: Throughout study up to week 48
Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
The original scale of HIV RNA viral load is between 30 copies/mL to infinitive. The minimum score of 30 is the lowest detectable value. The summary table categorized this continuous value to a dichotomous variable (<30 copies/mL and >= 30 copies/mL).
Measured: At baseline and week 24
Changes in Instrumental Activities of Daily Living Questionnaire
The Instrumental Activities of Daily Living (IADL) questionnaire is designed to learn more about how subjects are able to perform common tasks. There are 16 common tasks. For each task, if the score at the time of evaluation is worse than the best in the past, an indicator of 1 is given. Otherwise, the indicator is 0. The overall IADL score is a sum of 16 indicators divided by 16; therefore, the range is between 0 and 1 and the lower score is better. The 24-week change of IADL score was changed into a categorical variable (no change/worse vs. better) at week 24 compare to baseline.
Measured: At baseline and week 24
Changes in Medication Management Test (Modified)
The medication management test (modified) is designed to assess participants' medication management ability and their own medications and management. It's the number of how many times participants correctly answered 16 questions. The score ranges between 0 and 16, and higher score indicates better medication management.
Measured: At baseline and weeks 24
Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Protein marker of oxidative stress (Ceramides, Monohexosylceramides, Dihydro Glycosyl Galceramides, and Dihexosylceramides). For all markers, the outcome is the 24 week change (week 24-baseline).
Measured: At pre-entry and Week 24
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
Protein markers of oxidative stress (Protein carbonyls) and markers of immune activation (TNF-a, IL-6,CXCL8, Hepatocyte growth factor, Osteopontin, sFAS, sFAS ligand, and CXCL12). For all markers, the outcome is the 24 week change (week 24-baseline).
Measured: At pre-entry and Week 24
Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only)
Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline).
Measured: At pre-entry and Week 24
Changes in Neurotransmitter Levels (Unit = uM Only)
Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline).
Measured: At pre-entry and Week 24
Changes in Alternate Psychomotor Function Z-Score
The alternate psychomotor function is defined as the mean of age, sex, education, and African-American ethnicity adjusted z scores of Trail Making Part A (TMA), and age and education adjusted z score of Symbol Digit (SYD). The outcome is the 24 week change in alternate psychomotor function z-score (week 24-baseline).
Measured: At baseline and week 24
Changes in Alternate Verbal Memory Z-Score
The alternate verbal memory was defined as a mean of age and education adjusted z score of trials 1 to 3 and delayed recall tests. The outcome is the 24 week change in alternate verbal memory z-score (week 24-baseline).
Measured: At baseline and week 24
Changes in Alternate Frontal Systems Z-Score
The alternate frontal systems was defined as a mean of age and education adjusted z score of Interference task, and age, sex, education, and African-American ethnicity adjusted z score of Trail Making Part B. The outcome was the 24 week change in alternate frontal systems z-score (week 24-baseline).
Measured: At baseline and week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2006 (estimated)
- Study startMar 2007
- Primary completionJan 2010
- Study completionJan 2010
Why it stopped: This study was terminated early due to futility.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
- Sponsor type
- Research network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Neurologic AIDS Research Consortium (NARC)
- Responsible party
- Sponsor
- Investigators
- Ned Sacktor, MD, Study chair, Department of Neurology, Johns Hopkins Bayview Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00361257
- Sponsor's protocol ID
- ACTG A5235
- Other IDs
- 1U01AI068636
- Status last verified
- Jan 2016
- First submitted
- 4 Aug 2006
- Last updated
- 5 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004 Dec;45(6):549-59. doi: 10.1111/j.1365-2559.2004.02004.x.
PubMed 15569045Ferrari S, Vento S, Monaco S, Cavallaro T, Cainelli F, Rizzuto N, Temesgen Z. Human immunodeficiency virus-associated peripheral neuropathies. Mayo Clin Proc. 2006 Feb;81(2):213-9. doi: 10.4065/81.2.213.
PubMed 16471077Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA. 2005 Apr 27;293(16):2003-11. doi: 10.1001/jama.293.16.2003.
PubMed 15855434Sacktor N, Miyahara S, Deng L, Evans S, Schifitto G, Cohen BA, Paul R, Robertson K, Jarocki B, Scarsi K, Coombs RW, Zink MC, Nath A, Smith E, Ellis RJ, Singer E, Weihe J, McCarthy S, Hosey L, Clifford DB; ACTG A5235 team. Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial. Neurology. 2011 Sep 20;77(12):1135-42. doi: 10.1212/WNL.0b013e31822f0412. Epub 2011 Sep 7.
PubMed 21900636Sacktor N, Miyahara S, Evans S, Schifitto G, Cohen B, Haughey N, Drewes JL, Graham D, Zink MC, Anderson C, Nath A, Pardo CA, McCarthy S, Hosey L, Clifford D; ACTG A5235 team. Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment. J Neurovirol. 2014 Dec;20(6):620-6. doi: 10.1007/s13365-014-0292-0. Epub 2014 Nov 7.
PubMed 25377444
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II, Randomized, Placebo-Controlled, Double-Blind Study of Minocycline in the Treatment of HIV-Associated Cognitive Impairment
- ClinicalTrials.gov ID
- NCT00361257
- Acronym / sponsor ID
- ACTG A5235
- Conditions
- HIV Infections
- Keywords
- Treatment Experienced
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This study was terminated early due to futility.
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Advancing Clinical Therapeutics Globally for HIV/AIDS and Other InfectionsResearch network
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), Neurologic AIDS Research Consortium (NARC)
- Study start
- Mar 2007
- Primary completion
- Jan 2010 (actual)
- Study completion
- Jan 2010 (actual)
- First posted
- 8 Aug 2006 (estimated)
- Results
- Posted 26 Jul 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the effectiveness of minocycline, an antibiotic, in lessening the decreased mental function sometimes caused by anti-HIV drugs.
Detailed description
Cognitive impairment, including disabling cognitive, behavioral, and social dysfunction, continues to be a major problem faced by HIV-infected people taking antiretroviral therapy (ART). Research is needed to develop treatment that can be given alongside ART to prevent or lessen cognitive impairment caused by ART. Minocycline, an antibiotic commonly used for the treatment of acne and rheumatoid arthritis, has demonstrated anti-inflammatory and neuroprotective properties in previous studies. This study will evaluate the effectiveness of 24-week therapy with minocycline in lessening the cognitive impairment of HIV infected adults taking ART.
This study will last at least 24 weeks and has two steps. Patients will be stratified by HIV viral load and their neurocognitive state at study screening. In Step I, patients will be randomly assigned to one of two groups. Group 1 participants will receive twice-daily minocycline for 24 weeks; Group 2 participants will receive placebo. At the end of Phase I, study participants will be offered to enter Step II; all participants in Step II will receive twice-daily minocycline for an additional 24 weeks.
There will be a total of 8 study visits: 5 visits for Step I (including the entry visit) and 3 visits for Step II. Medical history will occur at all visits. Blood collection will occur at all visits. Participants who have positive nonreactive rapid plasma regain (RPR) values at screening will have mandatory lumbar punctures; for those with negative serum RPR results lumbar punctures are optional. Participants who test positive for syphilis will also have a lumbar puncture at their discretion to determine if syphilis has affected the brain. A neurological exam, other neuropsychological, dementia, and depression scale assessments, and urine collection will occur at most visits. Patients will be asked to complete a questionnaire on daily living at study entry and Weeks 12 and 24. Patients who have a lumbar puncture at Week 24 will receive a phone call 2 to 5 days after the procedure to report any adverse effects. Some participants may also have an electrocardiogram (ECG) during the study. For participants not on atazanavir some procedures and sample collections are optional.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1: Minocycline | Experimental | Drug: Minocycline100 mg orally every 12 hours |
| Arm 2: Matching placebo | Placebo comparator | Drug: Placebo (Tetracycline)orally every 12 hours |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- HIV infected
- Currently on a stable ART regimen for at least 16 consecutive weeks prior to study entry. Participants whose regimens have changed with respect to dose or formulation are eligible, but patients who have changed to different drugs in the same class are not eligible. Participants taking atazanavir must also be taking ritonavir or a ritonavir-boosted drug to be eligible for this study. More information on this criterion can be found in the protocol.
- Plan to stay on current ART regimen between study screening and Week 24
- AIDS Dementia Scale (ADC) Stage greater than 0
- Cognitive impairment, as evidenced by neuropsychological tests administered at screening
Key exclusion criteria (18 listed)
- Current cancers. Patients with basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or cancer not requiring systemic chemotherapy are not excluded.
- Severe premorbid psychiatric illness, including schizophrenia and major depression, which, in the opinion of the investigator, may interfere with the study
- Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
- Previous or current confounding neurological disorders. More information on this criterion can be found in the protocol.
- Central nervous system infections or cancers. More information on this criterion can be found in the protocol.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MinocyclineTetracycline antibiotic, 100 mg taken orally every 12 hours | Drug | Arm 1: Minocycline |
| Placebo (Tetracycline)Tetracycline antibiotic placebo, orally every 12 hours | Drug | Arm 2: Matching placebo |
Primary outcome
Change in Cognitive Performance Compared to Baseline
Time frame: At baseline and week 24
Th cognitive performance is measured by NPZ-8. NPZ-8 is defined as the average of age and education adjusted z-scores of eight neuropsychological tests subcomponents in the neuropsychological test battery. These eight tests are: 1. Grooved Pegboard Dominant Hand (GPD) 2. Grooved Pegboard Non-dominant hand (GPN) 3. Choice Reaction Time (CRT) 4. Sequential Reaction Time (QRT) 5. Timed Gait (TIG) 6. Trail Making Part A (TMA) 7. Trail Making Part B (TMB) 8. Symbol Digit (SYD) The primary outcome is NPZ-8 score at week24 - NPZ-8 score at baseline.
23 secondary outcomes
Change in Global Deficit Z-Score (GDS)
Time frame: At baseline and week 24
Change in Investigator's Clinical Global Impression Score (ICGIS)
Time frame: At week 24
Change in Cognitive Gross Motor Function Domain Z-Score
Time frame: At baseline and week 24
Change in Fine Motor Function Domain Z-Score
Time frame: At baseline and week 24
Change in Psychomotor Function Domain Z-Score
Time frame: At baseline and week 24
Change in Fine Motor/Nonverbal Function Domain Z-Score
Time frame: At baseline and week 24
Change in Information Processing Function Domain Z-Score
Time frame: At baseline and week 24
Change in Verbal Memory Domain Z-Score
Time frame: At baseline and week 24
Change in Frontal Systems Function Domain Z-Score
Time frame: At baseline and week 24
Change in Karnofsky Performance Score
Time frame: At baseline and week 24
Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks)
Time frame: At baseline and weeks 24
Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks)
Time frame: At baseline and week 24
Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
Time frame: Throughout study up to week 48
Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
Time frame: At baseline and week 24
Changes in Instrumental Activities of Daily Living Questionnaire
Time frame: At baseline and week 24
Changes in Medication Management Test (Modified)
Time frame: At baseline and weeks 24
Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Time frame: At pre-entry and Week 24
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
Time frame: At pre-entry and Week 24
Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only)
Time frame: At pre-entry and Week 24
Changes in Neurotransmitter Levels (Unit = uM Only)
Time frame: At pre-entry and Week 24
Changes in Alternate Psychomotor Function Z-Score
Time frame: At baseline and week 24
Changes in Alternate Verbal Memory Z-Score
Time frame: At baseline and week 24
Changes in Alternate Frontal Systems Z-Score
Time frame: At baseline and week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15569045Bell JE. An update on the neuropathology of HIV in the HAART era. Histopathology. 2004 Dec;45(6):549-59. doi: 10.1111/j.1365-2559.2004.02004.x.
- Background: PubMed 16471077Ferrari S, Vento S, Monaco S, Cavallaro T, Cainelli F, Rizzuto N, Temesgen Z. Human immunodeficiency virus-associated peripheral neuropathies. Mayo Clin Proc. 2006 Feb;81(2):213-9. doi: 10.4065/81.2.213.
- Background: PubMed 15855434Zink MC, Uhrlaub J, DeWitt J, Voelker T, Bullock B, Mankowski J, Tarwater P, Clements J, Barber S. Neuroprotective and anti-human immunodeficiency virus activity of minocycline. JAMA. 2005 Apr 27;293(16):2003-11. doi: 10.1001/jama.293.16.2003.
- Results publication: PubMed 21900636Sacktor N, Miyahara S, Deng L, Evans S, Schifitto G, Cohen BA, Paul R, Robertson K, Jarocki B, Scarsi K, Coombs RW, Zink MC, Nath A, Smith E, Ellis RJ, Singer E, Weihe J, McCarthy S, Hosey L, Clifford DB; ACTG A5235 team. Minocycline treatment for HIV-associated cognitive impairment: results from a randomized trial. Neurology. 2011 Sep 20;77(12):1135-42. doi: 10.1212/WNL.0b013e31822f0412. Epub 2011 Sep 7.
- Results publication: PubMed 25377444Sacktor N, Miyahara S, Evans S, Schifitto G, Cohen B, Haughey N, Drewes JL, Graham D, Zink MC, Anderson C, Nath A, Pardo CA, McCarthy S, Hosey L, Clifford D; ACTG A5235 team. Impact of minocycline on cerebrospinal fluid markers of oxidative stress, neuronal injury, and inflammation in HIV-seropositive individuals with cognitive impairment. J Neurovirol. 2014 Dec;20(6):620-6. doi: 10.1007/s13365-014-0292-0. Epub 2014 Nov 7.
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Prescribe to Prevent HIV: A Hybrid Trial Helping Addiction Clinics Prevent HIV & Infections Through Safer Drug Use Support
People Who Use Opioids/People With Opioid Use Disorder (OUD)
Recruiting
Evaluating the Impact of Using the B-OK Bottles for HIV and ART Literacy in South Africa
HIV, HIV Treatment
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
RecruitingObservational study
Olfactory Function and Model-Based Behavior in People Living With HIV and SUD
HIV, Substance Use Disorder
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ned Sacktor, MD study chair
Department of Neurology, Johns Hopkins Bayview Medical Center
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Minocycline in people with HIV Infections, run by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections at 16 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Jul 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Cognitive Performance Compared to Baseline (time frame: At baseline and week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00361257, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2016.