Trial Outcomes & Findings for Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults (NCT NCT00361257)
NCT ID: NCT00361257
Last Updated: 2016-02-05
Results Overview
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.
TERMINATED
PHASE2
107 participants
At baseline and week 24
2016-02-05
Participant Flow
Participant milestones
| Measure |
Minocycline
100 mg orally every 12 hours
|
Matching Placebo
Placebo taken orally every 12 hours
|
|---|---|---|
|
Step 1: Minocycline vs. Placebo
STARTED
|
52
|
55
|
|
Step 1: Minocycline vs. Placebo
COMPLETED
|
40
|
43
|
|
Step 1: Minocycline vs. Placebo
NOT COMPLETED
|
12
|
12
|
|
Step 2: Minocycline(Open Label) for All
STARTED
|
28
|
34
|
|
Step 2: Minocycline(Open Label) for All
COMPLETED
|
13
|
19
|
|
Step 2: Minocycline(Open Label) for All
NOT COMPLETED
|
15
|
15
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Minocycline for the Treatment of Decreased Mental Function in HIV-Infected Adults
Baseline characteristics by cohort
| Measure |
Minocycline
n=52 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=55 Participants
Placebo taken orally every 12 hours
|
Total
n=107 Participants
Total of all reporting groups
|
|---|---|---|---|
|
HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL)
CSF RNA VL <30 copies/mL
|
20 participants
n=5 Participants
|
18 participants
n=7 Participants
|
38 participants
n=5 Participants
|
|
HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL)
missing
|
31 participants
n=5 Participants
|
35 participants
n=7 Participants
|
66 participants
n=5 Participants
|
|
Central Nervous System (CNS) Penetration Score
|
7 Scores on a scale
STANDARD_DEVIATION 3 • n=5 Participants
|
7 Scores on a scale
STANDARD_DEVIATION 3 • n=7 Participants
|
7 Scores on a scale
STANDARD_DEVIATION 3 • n=5 Participants
|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
52 Participants
n=5 Participants
|
54 Participants
n=7 Participants
|
106 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Age, Continuous
|
50 years
STANDARD_DEVIATION 7 • n=5 Participants
|
52 years
STANDARD_DEVIATION 7 • n=7 Participants
|
51 years
STANDARD_DEVIATION 7 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
47 Participants
n=5 Participants
|
42 Participants
n=7 Participants
|
89 Participants
n=5 Participants
|
|
Cognitive Performance Score NPZ-8
|
-0.75 z-score
STANDARD_DEVIATION 0.90 • n=5 Participants
|
-1.03 z-score
STANDARD_DEVIATION 0.98 • n=7 Participants
|
-0.90 z-score
STANDARD_DEVIATION 0.95 • n=5 Participants
|
|
Global Deficit Z-Score (GDS)
|
-0.86 z-score
STANDARD_DEVIATION 0.72 • n=5 Participants
|
-1.08 z-score
STANDARD_DEVIATION 0.90 • n=7 Participants
|
-0.97 z-score
STANDARD_DEVIATION 0.82 • n=5 Participants
|
|
Cognitive Gross Motor Function Domain Z-Score
|
-2.44 z-score
STANDARD_DEVIATION 3.10 • n=5 Participants
|
-3.66 z-score
STANDARD_DEVIATION 4.16 • n=7 Participants
|
-3.06 z-score
STANDARD_DEVIATION 3.71 • n=5 Participants
|
|
Fine Motor Function Domain Z-Score
|
-0.35 z-score
STANDARD_DEVIATION 0.96 • n=5 Participants
|
-0.73 z-score
STANDARD_DEVIATION 0.99 • n=7 Participants
|
-0.55 z-score
STANDARD_DEVIATION 0.99 • n=5 Participants
|
|
Psychomotor Function Domain Z-Score
|
0.15 z-score
STANDARD_DEVIATION 1.00 • n=5 Participants
|
0.04 z-score
STANDARD_DEVIATION 1.03 • n=7 Participants
|
0.10 z-score
STANDARD_DEVIATION 1.01 • n=5 Participants
|
|
Fine Motor/Nonverbal Function Domain Z-Score
|
-1.11 z-score
STANDARD_DEVIATION 1.15 • n=5 Participants
|
-1.24 z-score
STANDARD_DEVIATION 1.18 • n=7 Participants
|
-1.18 z-score
STANDARD_DEVIATION 1.16 • n=5 Participants
|
|
Information Processing Function Domain Z-Score
|
-1.05 z-score
STANDARD_DEVIATION 1.52 • n=5 Participants
|
-1.03 z-score
STANDARD_DEVIATION 1.49 • n=7 Participants
|
-1.04 z-score
STANDARD_DEVIATION 1.50 • n=5 Participants
|
|
Verbal Memory Domain Z-Score
|
-1.33 z-score
STANDARD_DEVIATION 1.16 • n=5 Participants
|
-1.41 z-score
STANDARD_DEVIATION 1.12 • n=7 Participants
|
-1.37 z-score
STANDARD_DEVIATION 1.14 • n=5 Participants
|
|
Frontal Systems Function Domain Z-Score
|
-0.79 z-score
STANDARD_DEVIATION 0.98 • n=5 Participants
|
-1.05 z-score
STANDARD_DEVIATION 1.57 • n=7 Participants
|
-0.92 z-score
STANDARD_DEVIATION 1.32 • n=5 Participants
|
|
Karnofsky Score
70
|
5 participants
n=5 Participants
|
0 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Karnofsky Score
80
|
13 participants
n=5 Participants
|
16 participants
n=7 Participants
|
29 participants
n=5 Participants
|
|
Karnofsky Score
90
|
21 participants
n=5 Participants
|
34 participants
n=7 Participants
|
55 participants
n=5 Participants
|
|
Karnofsky Score
100
|
8 participants
n=5 Participants
|
5 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
Karnofsky Score
missing
|
5 participants
n=5 Participants
|
0 participants
n=7 Participants
|
5 participants
n=5 Participants
|
|
Cluster of Differentiation 4 (CD4)
|
551.65 copies/mm^3
STANDARD_DEVIATION 312.96 • n=5 Participants
|
535.49 copies/mm^3
STANDARD_DEVIATION 253.11 • n=7 Participants
|
543.35 copies/mm^3
STANDARD_DEVIATION 282.53 • n=5 Participants
|
|
Cluster of Differentiation 8 (CD8)
|
925.58 copies/mm^3
STANDARD_DEVIATION 370.48 • n=5 Participants
|
838.78 copies/mm^3
STANDARD_DEVIATION 353.73 • n=7 Participants
|
880.96 copies/mm^3
STANDARD_DEVIATION 362.88 • n=5 Participants
|
|
HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads
Plasma RNA VL >=30 copies/mL
|
7 participants
n=5 Participants
|
6 participants
n=7 Participants
|
13 participants
n=5 Participants
|
|
HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads
Plasma RNA VL < 30 copies/mL
|
42 participants
n=5 Participants
|
41 participants
n=7 Participants
|
83 participants
n=5 Participants
|
|
HIV-1 Plasma RiboNucleic Acid (RNA) Viral Loads
missing
|
3 participants
n=5 Participants
|
8 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
HIV-1 CerebroSpinal Fluid (CSF) RNA Viral Loads (VL)
CSF RNA VL >=30 copies/mL
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline
CSF RNA VL < 30 copies/mL
|
21 participants
n=5 Participants
|
22 participants
n=7 Participants
|
43 participants
n=5 Participants
|
|
Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline
CSF RNA VL >= 30 copies/mL
|
3 participants
n=5 Participants
|
4 participants
n=7 Participants
|
7 participants
n=5 Participants
|
|
Stratification Variable 1 - CSF Viral Load (VL) - Pre-baseline
No Lumbar Punctures (LPs)
|
28 participants
n=5 Participants
|
29 participants
n=7 Participants
|
57 participants
n=5 Participants
|
|
Stratification Variable 2 - Objective or subjective Neuropsychological test - Pre-baseline
Objective Neuropsychological (NP) Test
|
5 participants
n=5 Participants
|
7 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Stratification Variable 2 - Objective or subjective Neuropsychological test - Pre-baseline
Subjective NP Test
|
47 participants
n=5 Participants
|
48 participants
n=7 Participants
|
95 participants
n=5 Participants
|
|
Instrumental Activities of Daily Living (IADL) Summary Score
|
0.12 Scores on a scale
STANDARD_DEVIATION 0.15 • n=5 Participants
|
0.13 Scores on a scale
STANDARD_DEVIATION 0.16 • n=7 Participants
|
0.12 Scores on a scale
STANDARD_DEVIATION 0.15 • n=5 Participants
|
|
Medication Management Test (MMT) Score
|
14.72 Scores on a scale
STANDARD_DEVIATION 1.41 • n=5 Participants
|
14.09 Scores on a scale
STANDARD_DEVIATION 2.52 • n=7 Participants
|
14.39 Scores on a scale
STANDARD_DEVIATION 2.08 • n=5 Participants
|
|
Alternate Psychomotor Function Z-Score
|
-0.54 z-score
STANDARD_DEVIATION 0.82 • n=5 Participants
|
-0.63 z-score
STANDARD_DEVIATION 0.92 • n=7 Participants
|
-0.58 z-score
STANDARD_DEVIATION 0.87 • n=5 Participants
|
|
Alternate Verbal Memory Z-Score
|
-1.33 z-score
STANDARD_DEVIATION 1.16 • n=5 Participants
|
-1.41 z-score
STANDARD_DEVIATION 1.12 • n=7 Participants
|
-1.37 z-score
STANDARD_DEVIATION 1.14 • n=5 Participants
|
|
Alternate Frontal Systems Z-Score
|
-0.04 z-score
STANDARD_DEVIATION 0.86 • n=5 Participants
|
-0.13 z-score
STANDARD_DEVIATION 1.09 • n=7 Participants
|
-0.09 z-score
STANDARD_DEVIATION 0.98 • n=5 Participants
|
PRIMARY outcome
Timeframe: At baseline and week 24Population: 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.
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.
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=48 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Cognitive Performance Compared to Baseline
|
0.12 z-score
Standard Deviation 0.71
|
0.17 z-score
Standard Deviation 0.67
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on the observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=48 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Global Deficit Z-Score (GDS)
|
0.11 z-score
Standard Deviation 0.58
|
0.09 z-score
Standard Deviation 0.51
|
SECONDARY outcome
Timeframe: At week 24Population: The analysis was based on observed data.
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.
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=45 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Investigator's Clinical Global Impression Score (ICGIS)
Worsened
|
4 participants
|
2 participants
|
|
Change in Investigator's Clinical Global Impression Score (ICGIS)
No Change
|
28 participants
|
31 participants
|
|
Change in Investigator's Clinical Global Impression Score (ICGIS)
Improved
|
9 participants
|
12 participants
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on the observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=42 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Cognitive Gross Motor Function Domain Z-Score
|
0.22 z-score
Standard Deviation 1.61
|
0.08 z-score
Standard Deviation 2.68
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=48 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Fine Motor Function Domain Z-Score
|
0.27 z-score
Standard Deviation 0.84
|
0.05 z-score
Standard Deviation 0.61
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=48 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Psychomotor Function Domain Z-Score
|
0.07 z-score
Standard Deviation 0.66
|
0.15 z-score
Standard Deviation 0.88
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=48 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Fine Motor/Nonverbal Function Domain Z-Score
|
-0.15 z-score
Standard Deviation 0.76
|
-0.07 z-score
Standard Deviation 0.92
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=40 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=45 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Information Processing Function Domain Z-Score
|
0.14 z-score
Standard Deviation 1.65
|
0.20 z-score
Standard Deviation 1.14
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=47 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Verbal Memory Domain Z-Score
|
0.18 z-score
Standard Deviation 0.96
|
0.02 z-score
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=47 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Frontal Systems Function Domain Z-Score
|
-0.04 z-score
Standard Deviation 0.78
|
0.21 z-score
Standard Deviation 1.05
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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.
Outcome measures
| Measure |
Minocycline
n=39 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=45 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change in Karnofsky Performance Score
No Change/Worse
|
33 participants
|
42 participants
|
|
Change in Karnofsky Performance Score
Better
|
6 participants
|
3 participants
|
SECONDARY outcome
Timeframe: At baseline and weeks 24Population: The analysis was based on observed data.
The outcome was the 24 week change in CD4 cell count (week 24-baseline).
Outcome measures
| Measure |
Minocycline
n=40 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=34 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Cluster of Differentiation 4 (CD4) Cell Counts (24 Weeks)
|
24.10 cells/mm^3
Standard Deviation 141.22
|
8.24 cells/mm^3
Standard Deviation 143.02
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
The outcome was the 24 week change of CD8 cell counts (week 24-baseline).
Outcome measures
| Measure |
Minocycline
n=40 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=34 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Cluster of Differentiation 8 (CD8) Cell Counts (24 Weeks)
|
43.90 cells/mm^3
Standard Deviation 244.51
|
0.00 cells/mm^3
Standard Deviation 253.18
|
SECONDARY outcome
Timeframe: Throughout study up to week 48Population: 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.
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.
Outcome measures
| Measure |
Minocycline
n=52 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=55 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
0 - 4 weeks
|
29 participants with an event
|
32 participants with an event
|
|
Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
4.01 - 12 weeks
|
5 participants with an event
|
3 participants with an event
|
|
Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
12.01 - 24 weeks
|
2 participants with an event
|
1 participants with an event
|
|
Number of Participants With Grade 2 or Higher Toxicity and/or Signs and Symptoms
24.01 - 48 weeks
|
1 participants with an event
|
2 participants with an event
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The summary statistics were based on observed data. No statistical analysis was conducted.
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).
Outcome measures
| Measure |
Minocycline
n=20 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=21 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
>= 30 copies/mL at base, >= 30 at week 24
|
1 participants
|
0 participants
|
|
Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
>= 30 copies/mL at base, < 30 at week 24
|
0 participants
|
2 participants
|
|
Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
< 30 copies/mL at base, >= 30 at week 24
|
2 participants
|
0 participants
|
|
Change of HIV Plasma RiboNucleic Acid (RNA) Viral Load
< 30 copies/mL at base, < 30 at week 24
|
17 participants
|
19 participants
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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.
Outcome measures
| Measure |
Minocycline
n=42 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=43 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Instrumental Activities of Daily Living Questionnaire
No Change/Worse
|
30 participants
|
32 participants
|
|
Changes in Instrumental Activities of Daily Living Questionnaire
Better
|
12 participants
|
11 participants
|
SECONDARY outcome
Timeframe: At baseline and weeks 24Population: The analysis was based on observed data.
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.
Outcome measures
| Measure |
Minocycline
n=43 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=46 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Medication Management Test (Modified)
|
0.16 scores on a scale
Standard Deviation 1.57
|
0.48 scores on a scale
Standard Deviation 2.00
|
SECONDARY outcome
Timeframe: At pre-entry and Week 24Population: Participants who were willing to receive the lumber punctures at week 0 and 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).
Outcome measures
| Measure |
Minocycline
n=6 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=8 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Ceramides (counts per second)
|
0.0007 counts per second
Interval -0.0001 to 0.006
|
-0.0051 counts per second
Interval -0.0177 to 0.0006
|
|
Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Monohexosylceramides (counts per second)
|
0.0013 counts per second
Interval -0.0007 to 0.033
|
-0.0066 counts per second
Interval -0.0279 to -0.0004
|
|
Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Dihydro Glycosyl Galceramides (counts per second)
|
0.0201 counts per second
Interval 0.0043 to 0.0355
|
-0.0048 counts per second
Interval -0.018 to -0.001
|
|
Changes in Protein Markers of Oxidative Stress (Unit = Counts Per Second Only)
Dihexosylceramides (counts per second)
|
0.0005 counts per second
Interval -0.0003 to 0.007
|
-0.0043 counts per second
Interval -0.009 to -0.0001
|
SECONDARY outcome
Timeframe: At pre-entry and Week 24Population: Participants who were willing to receive the lumber punctures at week 0 and 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).
Outcome measures
| Measure |
Minocycline
n=8 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=13 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
Protein carbonyls (pg/ml)
|
4.0 pg/mL
Interval 3.32 to 82.29
|
13.2 pg/mL
Interval 0.13 to 39.74
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
TNF-α (pg/mL)
|
0.04 pg/mL
Interval 0.0 to 0.31
|
0.14 pg/mL
Interval 0.0 to 0.65
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
IL-6 (pg/mL)
|
-0.29 pg/mL
Interval -0.67 to 2.58
|
0.95 pg/mL
Interval -0.79 to 2.41
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
CXCL8 (pg/mL)
|
0.34 pg/mL
Interval -3.07 to 5.97
|
-6.13 pg/mL
Interval -12.5 to 3.07
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
Hepatocyte growth factor (pg/mL)
|
16.09 pg/mL
Interval -21.54 to 168.99
|
90.48 pg/mL
Interval 6.7 to 250.39
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
Osteopontin (pg/mL)
|
-5208.94 pg/mL
Interval -11579.9 to 7088.79
|
673.55 pg/mL
Interval -14689.54 to 23344.1
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
sFAS (pg/mL)
|
0.68 pg/mL
Interval -9.35 to 77.79
|
134.1 pg/mL
Interval 26.41 to 279.87
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
sFAS ligand (pg/mL)
|
-0.27 pg/mL
Interval -0.65 to 0.06
|
0.11 pg/mL
Interval -0.07 to 1.47
|
|
Changes in Markers of Oxidative Stress and Immune Activation (Unit=pg/mL Only)
CXCL12 (pg/mL)
|
204.39 pg/mL
Interval -164.2 to 1152.41
|
1,071.84 pg/mL
Interval -96.75 to 1678.84
|
SECONDARY outcome
Timeframe: At pre-entry and Week 24Population: Participants who were willing to receive the lumber punctures at week 0 and 24.
Protein marker of oxidative stress (Neurofilament heavy polypeptide). The outcome is the 24 week change (week 24-baseline).
Outcome measures
| Measure |
Minocycline
n=5 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=5 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Markers of Oxidative Stress (Unit = Pixels/mm2 Only)
|
-59.3 Pixels/mm^2
Interval -76.05 to -36.69
|
-3.04 Pixels/mm^2
Interval -6.31 to 59.86
|
SECONDARY outcome
Timeframe: At pre-entry and Week 24Population: Participants who were willing to receive the lumber punctures at week 0 and 24.
Neurotransmitter levels (Glutamate, Tryptophan, Anthranilic Acid, Quinolinic Acid, Kynurenin, and 3-Hydroxykynurenine). The outcome is the 24 week change (week 24-baseline).
Outcome measures
| Measure |
Minocycline
n=4 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=6 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Neurotransmitter Levels (Unit = uM Only)
Glutamate (uM)
|
5.09 uM
Interval -11.01 to 13.41
|
-1.08 uM
Interval -1.2 to 10.88
|
|
Changes in Neurotransmitter Levels (Unit = uM Only)
Tryptophan (uM)
|
-0.21 uM
Interval -0.78 to 0.12
|
0.07 uM
Interval 0.05 to 0.21
|
|
Changes in Neurotransmitter Levels (Unit = uM Only)
Anthranilic Acid (uM)
|
0.0 uM
Interval -2.25 to 10.87
|
0.0 uM
Interval -7.14 to 6.15
|
|
Changes in Neurotransmitter Levels (Unit = uM Only)
Quinolinic Acid (uM)
|
-0.55 uM
Interval -7.94 to 0.0
|
0.0 uM
Interval -9.07 to 4.11
|
|
Changes in Neurotransmitter Levels (Unit = uM Only)
Kynurenin (uM)
|
6.85 uM
Interval 0.01 to 46.75
|
6.97 uM
Interval 0.0 to 23.9
|
|
Changes in Neurotransmitter Levels (Unit = uM Only)
3-Hydroxykynurenine (uM)
|
-4.09 uM
Interval -11.51 to 0.02
|
-0.83 uM
Interval -5.97 to 0.0
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on the observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=48 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Alternate Psychomotor Function Z-Score
|
-0.03 z-score
Standard Deviation 0.66
|
0.05 z-score
Standard Deviation 0.76
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis is based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=47 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Alternate Verbal Memory Z-Score
|
0.18 z-score
Standard Deviation 0.96
|
0.02 z-score
Standard Deviation 1.10
|
SECONDARY outcome
Timeframe: At baseline and week 24Population: The analysis was based on observed data.
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).
Outcome measures
| Measure |
Minocycline
n=41 Participants
100 mg orally every 12 hours
|
Matching Placebo
n=47 Participants
Placebo taken orally every 12 hours
|
|---|---|---|
|
Changes in Alternate Frontal Systems Z-Score
|
0.03 z-score
Standard Deviation 0.67
|
-0.07 z-score
Standard Deviation 0.70
|
Adverse Events
Minocycline
Matching Placebo
Serious adverse events
| Measure |
Minocycline
n=52 participants at risk
100 mg orally every 12 hours
|
Matching Placebo
n=55 participants at risk
Placebo taken orally every 12 hours
|
|---|---|---|
|
Blood and lymphatic system disorders
Blood amylase increased
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
|
Nervous system disorders
Vocal cord paralysis
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
|
Renal and urinary disorders
Renal failure
|
0.00%
0/52 • Up to 48 weeks since the randomization.
|
1.8%
1/55 • Number of events 1 • Up to 48 weeks since the randomization.
|
|
Skin and subcutaneous tissue disorders
Basal cell carcinoma
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
|
General disorders
Tooth infection
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
|
Psychiatric disorders
Suicidal ideation
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
|
Psychiatric disorders
Suicidal attempt
|
0.00%
0/52 • Up to 48 weeks since the randomization.
|
1.8%
1/55 • Number of events 1 • Up to 48 weeks since the randomization.
|
|
General disorders
Hypertension
|
0.00%
0/52 • Up to 48 weeks since the randomization.
|
1.8%
1/55 • Number of events 1 • Up to 48 weeks since the randomization.
|
|
Blood and lymphatic system disorders
Blood triglycerides increased
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
|
Hepatobiliary disorders
Alanine aminotransferase increased
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
0.00%
0/55 • Up to 48 weeks since the randomization.
|
Other adverse events
| Measure |
Minocycline
n=52 participants at risk
100 mg orally every 12 hours
|
Matching Placebo
n=55 participants at risk
Placebo taken orally every 12 hours
|
|---|---|---|
|
General disorders
Fatigue
|
7.7%
4/52 • Number of events 4 • Up to 48 weeks since the randomization.
|
5.5%
3/55 • Number of events 3 • Up to 48 weeks since the randomization.
|
|
General disorders
Pain
|
9.6%
5/52 • Number of events 9 • Up to 48 weeks since the randomization.
|
16.4%
9/55 • Number of events 9 • Up to 48 weeks since the randomization.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
3.8%
2/52 • Number of events 2 • Up to 48 weeks since the randomization.
|
7.3%
4/55 • Number of events 4 • Up to 48 weeks since the randomization.
|
|
General disorders
Sob
|
0.00%
0/52 • Up to 48 weeks since the randomization.
|
7.3%
4/55 • Number of events 4 • Up to 48 weeks since the randomization.
|
|
Gastrointestinal disorders
Diarrhea/Loose
|
9.6%
5/52 • Number of events 5 • Up to 48 weeks since the randomization.
|
5.5%
3/55 • Number of events 3 • Up to 48 weeks since the randomization.
|
|
Gastrointestinal disorders
Nausea
|
3.8%
2/52 • Number of events 2 • Up to 48 weeks since the randomization.
|
7.3%
4/55 • Number of events 4 • Up to 48 weeks since the randomization.
|
|
General disorders
Headache
|
1.9%
1/52 • Number of events 1 • Up to 48 weeks since the randomization.
|
12.7%
7/55 • Number of events 7 • Up to 48 weeks since the randomization.
|
Additional Information
ACTG Clinicaltrials.gov Coordinator
ACTG Network Coordinating Center, Social and Scientific Systems, Inc.
Results disclosure agreements
- Principal investigator is a sponsor employee In accordance with the Clinical Trial Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
- Publication restrictions are in place
Restriction type: OTHER