HIV Infections
Conditions
Keywords
Treatment Experienced
Brief 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.
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.
Interventions
DRUGMinocycline
Tetracycline antibiotic, 100 mg taken orally every 12 hours
DRUGPlacebo (Tetracycline)
Tetracycline antibiotic placebo, orally every 12 hours
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Neurologic AIDS Research Consortium (NARC)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* 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. * 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
Exclusion criteria
* 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 * 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognitive Performance Compared to Baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Investigator's Clinical Global Impression Score (ICGIS) | At week 24 | 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. |
| Change in Cognitive Gross Motor Function Domain Z-Score | At baseline and week 24 | 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). |
| Change in Fine Motor Function Domain Z-Score | At baseline and week 24 | 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). |
| Change in Psychomotor Function Domain Z-Score | At baseline and week 24 | 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). |
| Change in Fine Motor/Nonverbal Function Domain Z-Score | At baseline and week 24 | 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). |
| Change in Information Processing Function Domain Z-Score | At baseline and week 24 | 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). |
| Change in Verbal Memory Domain Z-Score | At baseline and week 24 | 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). |
| Change in Frontal Systems Function Domain Z-Score | At baseline and week 24 | 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). |
| Change in Karnofsky Performance Score | At baseline and week 24 | 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. |
| Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks) | At baseline and weeks 24 | The outcome was the 24 week change in CD4 cell count (week 24-baseline). |
| Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks) | At baseline and week 24 | The outcome was the 24 week change of CD8 cell counts (week 24-baseline). |
| Change in Global Deficit Z-Score (GDS) | At baseline and week 24 | 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). |
| Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | At baseline and week 24 | 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). |
| Changes in Instrumental Activities of Daily Living Questionnaire | At baseline and week 24 | 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. |
| Changes in Medication Management Test (Modified) | At baseline and weeks 24 | 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. |
| Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | At pre-entry and Week 24 | 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). |
| Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | At pre-entry and Week 24 | 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). |
| Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only) | At pre-entry and Week 24 | Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline). |
| Changes in Neurotransmitter Levels (Unit = uM Only) | At pre-entry and Week 24 | Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline). |
| Changes in Alternate Psychomotor Function Z-Score | At baseline and week 24 | 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). |
| Changes in Alternate Verbal Memory Z-Score | At baseline and week 24 | 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). |
| Changes in Alternate Frontal Systems Z-Score | At baseline and week 24 | 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). |
| Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | Throughout study up to week 48 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Minocycline 100 mg orally every 12 hours | 52 |
| Matching Placebo Placebo taken orally every 12 hours | 55 |
| Total | 107 |
Baseline characteristics
| Characteristic | Matching Placebo | Minocycline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 54 Participants | 52 Participants | 106 Participants |
| Age, Continuous | 52 years STANDARD_DEVIATION 7 | 50 years STANDARD_DEVIATION 7 | 51 years STANDARD_DEVIATION 7 |
| Alternate Frontal Systems Z-Score | -0.13 z-score STANDARD_DEVIATION 1.09 | -0.04 z-score STANDARD_DEVIATION 0.86 | -0.09 z-score STANDARD_DEVIATION 0.98 |
| Alternate Psychomotor Function Z-Score | -0.63 z-score STANDARD_DEVIATION 0.92 | -0.54 z-score STANDARD_DEVIATION 0.82 | -0.58 z-score STANDARD_DEVIATION 0.87 |
| Alternate Verbal Memory Z-Score | -1.41 z-score STANDARD_DEVIATION 1.12 | -1.33 z-score STANDARD_DEVIATION 1.16 | -1.37 z-score STANDARD_DEVIATION 1.14 |
| Central Nervous System (CNS) Penetration Score | 7 Scores on a scale STANDARD_DEVIATION 3 | 7 Scores on a scale STANDARD_DEVIATION 3 | 7 Scores on a scale STANDARD_DEVIATION 3 |
| Cluster of Differentiation 4 (CD4) | 535.49 copies/mm^3 STANDARD_DEVIATION 253.11 | 551.65 copies/mm^3 STANDARD_DEVIATION 312.96 | 543.35 copies/mm^3 STANDARD_DEVIATION 282.53 |
| Cluster of Differentiation 8 (CD8) | 838.78 copies/mm^3 STANDARD_DEVIATION 353.73 | 925.58 copies/mm^3 STANDARD_DEVIATION 370.48 | 880.96 copies/mm^3 STANDARD_DEVIATION 362.88 |
| Cognitive Gross Motor Function Domain Z-Score | -3.66 z-score STANDARD_DEVIATION 4.16 | -2.44 z-score STANDARD_DEVIATION 3.1 | -3.06 z-score STANDARD_DEVIATION 3.71 |
| Cognitive Performance Score NPZ-8 | -1.03 z-score STANDARD_DEVIATION 0.98 | -0.75 z-score STANDARD_DEVIATION 0.9 | -0.90 z-score STANDARD_DEVIATION 0.95 |
| Fine Motor Function Domain Z-Score | -0.73 z-score STANDARD_DEVIATION 0.99 | -0.35 z-score STANDARD_DEVIATION 0.96 | -0.55 z-score STANDARD_DEVIATION 0.99 |
| Fine Motor/Nonverbal Function Domain Z-Score | -1.24 z-score STANDARD_DEVIATION 1.18 | -1.11 z-score STANDARD_DEVIATION 1.15 | -1.18 z-score STANDARD_DEVIATION 1.16 |
| Frontal Systems Function Domain Z-Score | -1.05 z-score STANDARD_DEVIATION 1.57 | -0.79 z-score STANDARD_DEVIATION 0.98 | -0.92 z-score STANDARD_DEVIATION 1.32 |
| Global Deficit Z-Score (GDS) | -1.08 z-score STANDARD_DEVIATION 0.9 | -0.86 z-score STANDARD_DEVIATION 0.72 | -0.97 z-score STANDARD_DEVIATION 0.82 |
| HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL) CSF RNA VL <30 copies/mL | 18 participants | 20 participants | 38 participants |
| HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL) CSF RNA VL >=30 copies/mL | 2 participants | 1 participants | 3 participants |
| HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL) missing | 35 participants | 31 participants | 66 participants |
| HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads missing | 8 participants | 3 participants | 11 participants |
| HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads Plasma RNA VL < 30 copies/mL | 41 participants | 42 participants | 83 participants |
| HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads Plasma RNA VL >=30 copies/mL | 6 participants | 7 participants | 13 participants |
| Information Processing Function Domain Z-Score | -1.03 z-score STANDARD_DEVIATION 1.49 | -1.05 z-score STANDARD_DEVIATION 1.52 | -1.04 z-score STANDARD_DEVIATION 1.5 |
| Instrumental Activities of Daily Living (IADL) Summary Score | 0.13 Scores on a scale STANDARD_DEVIATION 0.16 | 0.12 Scores on a scale STANDARD_DEVIATION 0.15 | 0.12 Scores on a scale STANDARD_DEVIATION 0.15 |
| Karnofsky Score 100 | 5 participants | 8 participants | 13 participants |
| Karnofsky Score 70 | 0 participants | 5 participants | 5 participants |
| Karnofsky Score 80 | 16 participants | 13 participants | 29 participants |
| Karnofsky Score 90 | 34 participants | 21 participants | 55 participants |
| Karnofsky Score missing | 0 participants | 5 participants | 5 participants |
| Medication Management Test (MMT) Score | 14.09 Scores on a scale STANDARD_DEVIATION 2.52 | 14.72 Scores on a scale STANDARD_DEVIATION 1.41 | 14.39 Scores on a scale STANDARD_DEVIATION 2.08 |
| Psychomotor Function Domain Z-Score | 0.04 z-score STANDARD_DEVIATION 1.03 | 0.15 z-score STANDARD_DEVIATION 1 | 0.10 z-score STANDARD_DEVIATION 1.01 |
| Sex: Female, Male Female | 13 Participants | 5 Participants | 18 Participants |
| Sex: Female, Male Male | 42 Participants | 47 Participants | 89 Participants |
| Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline CSF RNA VL < 30 copies/mL | 22 participants | 21 participants | 43 participants |
| Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline CSF RNA VL >= 30 copies/mL | 4 participants | 3 participants | 7 participants |
| Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline No Lumbar Punctures (LPs) | 29 participants | 28 participants | 57 participants |
| Stratification Variable 2 - Objective or subjective Neuropsychological test - Pre-baseline Objective Neuropsychological (NP) Test | 7 participants | 5 participants | 12 participants |
| Stratification Variable 2 - Objective or subjective Neuropsychological test - Pre-baseline Subjective NP Test | 48 participants | 47 participants | 95 participants |
| Verbal Memory Domain Z-Score | -1.41 z-score STANDARD_DEVIATION 1.12 | -1.33 z-score STANDARD_DEVIATION 1.16 | -1.37 z-score STANDARD_DEVIATION 1.14 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 18 / 52 | 34 / 55 |
| serious Total, serious adverse events | 7 / 52 | 3 / 55 |
Outcome results
Primary
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: 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.
Time frame: At baseline and week 24
Population: The descriptive statistics above were based on the observed data; however, the statistical analysis was conducted by the ITT analysis and the missing outcomes at week 24 were imputed based on multiple regression imputations.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Cognitive Performance Compared to Baseline | 0.12 z-score | Standard Deviation 0.71 |
| Matching Placebo | Change in Cognitive Performance Compared to Baseline | 0.17 z-score | Standard Deviation 0.67 |
Comparison: The null hypothesis was that the 24-week change of NPZ-8 in the minocycline group was the same as the one in the placebo group.p-value: 0.65195% CI: [-0.258, 0.386]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on the observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Cognitive Gross Motor Function Domain Z-Score | 0.22 z-score | Standard Deviation 1.61 |
| Matching Placebo | Change in Cognitive Gross Motor Function Domain Z-Score | 0.08 z-score | Standard Deviation 2.68 |
Comparison: The null hypothesis is that the 24 week change in the cognitive gross motor function domain score in the minocycline group is the same as the one in the placebo group.p-value: 0.24395% CI: [-0.349, 1.354]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Fine Motor Function Domain Z-Score | 0.27 z-score | Standard Deviation 0.84 |
| Matching Placebo | Change in Fine Motor Function Domain Z-Score | 0.05 z-score | Standard Deviation 0.61 |
Comparison: The null hypothesis was that the 24 week change in fine motor function domain score in the minocycline group was the same as the one in the placebo group.p-value: 0.05995% CI: [-0.011, 0.596]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Fine Motor/Nonverbal Function Domain Z-Score | -0.15 z-score | Standard Deviation 0.76 |
| Matching Placebo | Change in Fine Motor/Nonverbal Function Domain Z-Score | -0.07 z-score | Standard Deviation 0.92 |
Comparison: The null hypothesis was that the 24 week change of fine motor/nonverbal function domain score in the minocycline group was the same as in the placebo group.p-value: 0.63795% CI: [-0.449, 0.276]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Frontal Systems Function Domain Z-Score | -0.04 z-score | Standard Deviation 0.78 |
| Matching Placebo | Change in Frontal Systems Function Domain Z-Score | 0.21 z-score | Standard Deviation 1.05 |
Comparison: The null hypothesis was that the 24 week change of frontal systems function domain score in the minocycline group was the same as the one in the placebo group.p-value: 0.46795% CI: [-0.467, 0.216]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on the observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Global Deficit Z-Score (GDS) | 0.11 z-score | Standard Deviation 0.58 |
| Matching Placebo | Change in Global Deficit Z-Score (GDS) | 0.09 z-score | Standard Deviation 0.51 |
Comparison: The null hypothesis was that the 24-week changes in Global Deficit Score (GDS) between the minocycline and placebo groups are the same.p-value: 0.43495% CI: [-0.14, 0.323]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Information Processing Function Domain Z-Score | 0.14 z-score | Standard Deviation 1.65 |
| Matching Placebo | Change in Information Processing Function Domain Z-Score | 0.20 z-score | Standard Deviation 1.14 |
Comparison: The null hypothesis was that the 24 week change of information processing function domain score in the minocycline group was the same as the one in the placebo group.p-value: 0.75495% CI: [-0.544, 0.396]Regression, Linear
Secondary
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.
Time frame: At week 24
Population: The analysis was based on observed data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Change in Investigator's Clinical Global Impression Score (ICGIS) | Worsened | 4 participants |
| Minocycline | Change in Investigator's Clinical Global Impression Score (ICGIS) | No Change | 28 participants |
| Minocycline | Change in Investigator's Clinical Global Impression Score (ICGIS) | Improved | 9 participants |
| Matching Placebo | Change in Investigator's Clinical Global Impression Score (ICGIS) | Worsened | 2 participants |
| Matching Placebo | Change in Investigator's Clinical Global Impression Score (ICGIS) | No Change | 31 participants |
| Matching Placebo | Change in Investigator's Clinical Global Impression Score (ICGIS) | Improved | 12 participants |
Comparison: The null hypothesis is that the 24 week changes of participants' clinical status in the minocycline group were the same as the ones in the placebo group based on ICGIS.p-value: 0.33795% CI: [0.625, 3.936]Regression, Cumulative Logistic
Secondary
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.
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Change in Karnofsky Performance Score | No Change/Worse | 33 participants |
| Minocycline | Change in Karnofsky Performance Score | Better | 6 participants |
| Matching Placebo | Change in Karnofsky Performance Score | No Change/Worse | 42 participants |
| Matching Placebo | Change in Karnofsky Performance Score | Better | 3 participants |
Comparison: The null hypothesis was that the proportion of being better at 24 weeks in minocycline group was the same as in the placebo group.p-value: 0.23495% CI: [0.575, 10.668]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Psychomotor Function Domain Z-Score | 0.07 z-score | Standard Deviation 0.66 |
| Matching Placebo | Change in Psychomotor Function Domain Z-Score | 0.15 z-score | Standard Deviation 0.88 |
Comparison: The null hypothesis was that the 24 change of psychomotor function domain score in the minocycline group is the same as in the placebo group.p-value: 0.57295% CI: [-0.375, 0.209]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Change in Verbal Memory Domain Z-Score | 0.18 z-score | Standard Deviation 0.96 |
| Matching Placebo | Change in Verbal Memory Domain Z-Score | 0.02 z-score | Standard Deviation 1.1 |
Comparison: The null hypothesis was that the 24 week change of verbal memory domain score in the minocycline group was the same as the one in the placebo group.p-value: 0.48495% CI: [-0.266, 0.558]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The summary statistics were based on observed data. No statistical analysis was conducted.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | >= 30 copies/mL at base, >= 30 at week 24 | 1 participants |
| Minocycline | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | >= 30 copies/mL at base, < 30 at week 24 | 0 participants |
| Minocycline | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | < 30 copies/mL at base, >= 30 at week 24 | 2 participants |
| Minocycline | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | < 30 copies/mL at base, < 30 at week 24 | 17 participants |
| Matching Placebo | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | < 30 copies/mL at base, < 30 at week 24 | 19 participants |
| Matching Placebo | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | >= 30 copies/mL at base, >= 30 at week 24 | 0 participants |
| Matching Placebo | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | < 30 copies/mL at base, >= 30 at week 24 | 0 participants |
| Matching Placebo | Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load | >= 30 copies/mL at base, < 30 at week 24 | 2 participants |
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Alternate Frontal Systems Z-Score | 0.03 z-score | Standard Deviation 0.67 |
| Matching Placebo | Changes in Alternate Frontal Systems Z-Score | -0.07 z-score | Standard Deviation 0.7 |
Comparison: The null hypothesis was the 24 week change of alternate frontal systems score in the minocycline group was the same as the one in the placebo group.p-value: 0.6995% CI: [-0.217, 0.327]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on the observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Alternate Psychomotor Function Z-Score | -0.03 z-score | Standard Deviation 0.66 |
| Matching Placebo | Changes in Alternate Psychomotor Function Z-Score | 0.05 z-score | Standard Deviation 0.76 |
Comparison: The null hypothesis was that the 24 week change in alternate psychomotor function score in the minocycline group was the same as the one in the placebo group.p-value: 0.50695% CI: [-0.388, 0.193]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis is based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Alternate Verbal Memory Z-Score | 0.18 z-score | Standard Deviation 0.96 |
| Matching Placebo | Changes in Alternate Verbal Memory Z-Score | 0.02 z-score | Standard Deviation 1.1 |
Comparison: The null hypothesis was that the 24 week change in the alternate verbal memory score in the minocycline group was the same as the one in the placebo group.p-value: 0.48495% CI: [-0.266, 0.558]Regression, Linear
Secondary
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).
Time frame: At baseline and weeks 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks) | 24.10 cells/mm^3 | Standard Deviation 141.22 |
| Matching Placebo | Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks) | 8.24 cells/mm^3 | Standard Deviation 143.02 |
Comparison: The null hypothesis was that the 24 week change in CD4 cell counts in the minocycline group was the same as the one in the placebo group.p-value: 0.57495% CI: [-48.26, 86.44]Regression, Linear
Secondary
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).
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks) | 43.90 cells/mm^3 | Standard Deviation 244.51 |
| Matching Placebo | Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks) | 0.00 cells/mm^3 | Standard Deviation 253.18 |
Comparison: The null hypothesis was that the 24 week change in CD8 cell count in the minocycline group was the same as the one in the placebo group.p-value: 0.50295% CI: [-79.12, 159.97]Regression, Linear
Secondary
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.
Time frame: At baseline and week 24
Population: The analysis was based on observed data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Changes in Instrumental Activities of Daily Living Questionnaire | No Change/Worse | 30 participants |
| Minocycline | Changes in Instrumental Activities of Daily Living Questionnaire | Better | 12 participants |
| Matching Placebo | Changes in Instrumental Activities of Daily Living Questionnaire | No Change/Worse | 32 participants |
| Matching Placebo | Changes in Instrumental Activities of Daily Living Questionnaire | Better | 11 participants |
Comparison: The null hypothesis was that the proportion of participants who got better at week 24 compared to baseline in the minocycline group was the same as the one in the placebo group.p-value: 0.8995% CI: [0.405, 2.837]Regression, Logistic
Secondary
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).
Time frame: At pre-entry and Week 24
Population: Participants who were willing to receive the lumber punctures at week 0 and 24.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | TNF-α (pg/mL) | 0.04 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Osteopontin (pg/mL) | -5208.94 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | CXCL8 (pg/mL) | 0.34 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | sFAS (pg/mL) | 0.68 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | IL-6 (pg/mL) | -0.29 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | sFAS ligand (pg/mL) | -0.27 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Hepatocyte growth factor (pg/mL) | 16.09 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | CXCL12 (pg/mL) | 204.39 pg/mL |
| Minocycline | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Protein carbonyls (pg/ml) | 4.0 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | CXCL12 (pg/mL) | 1,071.84 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Protein carbonyls (pg/ml) | 13.2 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | TNF-α (pg/mL) | 0.14 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | IL-6 (pg/mL) | 0.95 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | CXCL8 (pg/mL) | -6.13 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Hepatocyte growth factor (pg/mL) | 90.48 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | Osteopontin (pg/mL) | 673.55 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | sFAS (pg/mL) | 134.1 pg/mL |
| Matching Placebo | Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only) | sFAS ligand (pg/mL) | 0.11 pg/mL |
Secondary
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).
Time frame: At pre-entry and Week 24
Population: Participants who were willing to receive the lumber punctures at week 0 and 24.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Minocycline | Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only) | -59.3 Pixels/mm^2 |
| Matching Placebo | Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only) | -3.04 Pixels/mm^2 |
Secondary
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.
Time frame: At baseline and weeks 24
Population: The analysis was based on observed data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Minocycline | Changes in Medication Management Test (Modified) | 0.16 scores on a scale | Standard Deviation 1.57 |
| Matching Placebo | Changes in Medication Management Test (Modified) | 0.48 scores on a scale | Standard Deviation 2 |
Comparison: The null hypothesis was that the 24 change of medication management test score in the minocycline group was the same as the one in the placebo group.p-value: 0.30495% CI: [-1.182, 0.373]Regression, Linear
Secondary
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).
Time frame: At pre-entry and Week 24
Population: Participants who were willing to receive the lumber punctures at week 0 and 24.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Minocycline | Changes in Neurotransmitter Levels (Unit = uM Only) | Glutamate (uM) | 5.09 uM |
| Minocycline | Changes in Neurotransmitter Levels (Unit = uM Only) | Tryptophan (uM) | -0.21 uM |
| Minocycline | Changes in Neurotransmitter Levels (Unit = uM Only) | Anthranilic Acid (uM) | 0.0 uM |
| Minocycline | Changes in Neurotransmitter Levels (Unit = uM Only) | Quinolinic Acid (uM) | -0.55 uM |
| Minocycline | Changes in Neurotransmitter Levels (Unit = uM Only) | Kynurenin (uM) | 6.85 uM |
| Minocycline | Changes in Neurotransmitter Levels (Unit = uM Only) | 3-Hydroxykynurenine (uM) | -4.09 uM |
| Matching Placebo | Changes in Neurotransmitter Levels (Unit = uM Only) | Kynurenin (uM) | 6.97 uM |
| Matching Placebo | Changes in Neurotransmitter Levels (Unit = uM Only) | Glutamate (uM) | -1.08 uM |
| Matching Placebo | Changes in Neurotransmitter Levels (Unit = uM Only) | Quinolinic Acid (uM) | 0.0 uM |
| Matching Placebo | Changes in Neurotransmitter Levels (Unit = uM Only) | Tryptophan (uM) | 0.07 uM |
| Matching Placebo | Changes in Neurotransmitter Levels (Unit = uM Only) | 3-Hydroxykynurenine (uM) | -0.83 uM |
| Matching Placebo | Changes in Neurotransmitter Levels (Unit = uM Only) | Anthranilic Acid (uM) | 0.0 uM |
Secondary
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).
Time frame: At pre-entry and Week 24
Population: Participants who were willing to receive the lumber punctures at week 0 and 24.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Minocycline | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Ceramides (counts per second) | 0.0007 counts per second |
| Minocycline | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Monohexosylceramides (counts per second) | 0.0013 counts per second |
| Minocycline | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Dihydro Glycosyl Galceramides (counts per second) | 0.0201 counts per second |
| Minocycline | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Dihexosylceramides (counts per second) | 0.0005 counts per second |
| Matching Placebo | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Dihexosylceramides (counts per second) | -0.0043 counts per second |
| Matching Placebo | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Ceramides (counts per second) | -0.0051 counts per second |
| Matching Placebo | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Dihydro Glycosyl Galceramides (counts per second) | -0.0048 counts per second |
| Matching Placebo | Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only) | Monohexosylceramides (counts per second) | -0.0066 counts per second |
Secondary
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.
Time frame: Throughout study up to week 48
Population: The analysis includes all randomized participants. A total of 37 minocycline and 38 placebo participants reported Grade 2 or higher toxicity and/or signs and symptoms during 48 weeks.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Minocycline | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 0 - 4 weeks | 29 participants with an event |
| Minocycline | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 4.01 - 12 weeks | 5 participants with an event |
| Minocycline | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 12.01 - 24 weeks | 2 participants with an event |
| Minocycline | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 24.01 - 48 weeks | 1 participants with an event |
| Matching Placebo | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 24.01 - 48 weeks | 2 participants with an event |
| Matching Placebo | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 0 - 4 weeks | 32 participants with an event |
| Matching Placebo | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 12.01 - 24 weeks | 1 participants with an event |
| Matching Placebo | Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms | 4.01 - 12 weeks | 3 participants with an event |
Comparison: The null hypothesis was that the time to Grade 2 or higher toxicity and/or signs and symptoms in the minocycline group was the same as the one in the placebo group.p-value: 0.967Log Rank