Minocycline for HIV+ Cognitive Impairment in Uganda
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Study Type:  Interventional 

Study Design:  Allocation: Randomized; Intervention Model: Single Group Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment 
Conditions: 
HIVassociated Cognitive Impairment HIV Infections 
Interventions: 
Drug: minocycline Drug: minocycline placebo capsule 
Participant Flow
Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations 

The recruitment period was from Mar 2008 to Oct 2009 when the study was stopped early (Data and Safety Monitoring Board (DSMB) decision based on futility) on Nov 2009. The study participants were recruited from the Infectious Disease Institute, Makerere University, Kampala, Uganda. 
PreAssignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment 

Total of 353 participants were screened; only 73 were randomized and thus 280 were not enrolled: 146 of them did not have cognitive impairment, 55 of them lacked laboratory inclusion criteria, and 79 of them had "others". 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Participant Flow for 2 periods
Period 1: Step1
Minocycline  Placebo  

STARTED  36  37 
COMPLETED  26  26 
NOT COMPLETED  10  11 
Early Study Closure  5  7 
Adverse Event  1  1 
Protocol Violation  1  0 
Pregnancy  1  0 
Withdrawal by Subject  2  3 
Period 2: Step2
Minocycline  Placebo  

STARTED  19 ^{[1] }  21 ^{[2] } 
COMPLETED  13  15 
NOT COMPLETED  6  6 
Early Study Closure  6  2 
Adverse Event  0  3 
Initiation of antiretroviral therapy/ART  0  1 
^{[1]}  26 participants completed STEP1; however, only 19 out of the 26 decided to enroll in STEP2. 

^{[2]}  26 participants completed STEP1; however, only 21 out of the 26 decided to enroll in STEP2. 
Baseline Characteristics
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

No text entered. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Total  Total of all reporting groups 
Baseline Measures
Minocycline  Placebo  Total  

Overall Participants Analyzed [Units: Participants] 
36  37  73  
Age [Units: Participants] 

<=18 years  0  0  0  
Between 18 and 65 years  36  37  73  
>=65 years  0  0  0  
Age [Units: Years] Mean (Standard Deviation) 
37.3 (8.21)  36.7 (7.17)  37.0 (7.66)  
Gender [Units: Participants] 

Female  34  32  66  
Male  2  5  7  
Region of Enrollment [Units: Participants] 

Uganda  36  37  73  
Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale ^{[1] } [Units: Participants] 

Equivocal/subclinical  35  37  72  
Mild  1  0  1  


Baseline Cluster of Differentiation Four (CD4) Count [Units: Cells/mm^3] Median (Full Range) 
319 (251 to 469) 
305 (252 to 500) 
313 (251 to 500) 

Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL)) [Units: copies/mL] Log Mean (InterQuartile Range) 
4.41 (4.09 to 4.94) 
4.59 (4.12 to 5.25) 
4.50 (4.10 to 5.10) 

Baseline Karnofsky's Performance Score ^{[1] } [Units: Participants] 

80 (Karnofsky Score)  1  2  3  
90 (Karnofsky Score)  35  34  69  
100 (Karnofsky Score)  0  1  1  


Baseline Instrumental Activities of Daily Living (IADL) ^{[1] } [Units: Participants] 

Primarily cognitive problems  1  0  1  
Primarily physical problems  6  2  8  
Not having any difficulties on the tasks  29  35  64  


Baseline Overall Neurological Assessment [Units: Participants] 

Normal neurological assessment  26  30  56  
Central Nervous System (CNS) abnormality only  4  5  9  
Peripheral Nervous System (PNS) abnormality only  4  1  5  
CNS and PNS abnormality  1  1  2  
Can not assess  1  0  1  
Baseline Uganda Neuropsychological Test Battery Summary measure (U NP Sum) ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
0.97 (0.78)  0.97 (0.86)  0.97 (0.82)  


WHOUCLA Auditory Verbal Learning Test (AVLT): Trials Total ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
1.28 (0.88)  1.48 (1.14)  1.38 (1.02)  


WHOUCLA Auditory Verbal Learning Test (AVLT): Delayed ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
1.17 (0.79)  1.15 (1.18)  1.16 (1.00)  


Color Trails 1 ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
1.35 (2.03)  1.65 (3.03)  1.51 (2.60)  


Color Trails 2 ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
2.55 (2.07)  2.33 (2.05)  2.44 (2.05)  


Grooved Pegboard Dominant ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
0.34 (1.58)  0.03 (1.14)  0.18 (1.37)  


Grooved Pegboard Nondominant ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
0.56 (1.82)  0.48 (1.42)  0.52 (1.61)  


Symbol Digit ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
0.87 (0.96)  0.86 (0.80)  0.86 (0.88)  


Digit Span Backward ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
0.68 (0.75)  0.94 (1.06)  0.81 (0.93)  


Digit Span Forward ^{[1] } [Units: Zscores] Mean (Standard Deviation) 
0.02 (0.79)  0.19 (0.99)  0.11 (0.90)  

Outcome Measures
1. Primary:  24week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) [ Time Frame: At baseline and week 24 ] 
Measure Type  Primary 

Measure Title  24week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) 
Measure Description  The U NP Sum is defined as the average of z scores for 9 neuropsychological test subcomponents in the neuropsychological test battery (i.e. the average of normadjusted ("z") scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Nondominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHOUCLA Verbal Learning test Trial 5, WHOUCLA Verbal Learning test delayed recall, Digit Span forward and Digit Span backward). The outcome is defined as U NP Sum at week 24  U NP Sum at baseline. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The descriptive statistics are based on per protocol analysis. For the statistical analysis, ITT analysis was used and the missing U NP Sums at week 24 were imputed using a multiple regression imputation method. The number of participants analyzed for the ITT analysis was 73 (36 for Minocycline and 37 for Placebo). 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
30  29 
24week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) [Units: Zscore] Mean (Standard Deviation) 
0.44 (0.74)  0.49 (0.67) 
Statistical Analysis 1 for 24week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Regression, Linear 
P Value ^{[4]}  0.370 
Slope ^{[5]}  0.026 
95% Confidence Interval  0.512 to 0.460 
Standard Error of the mean  (0.248) 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis was that the 24week changes of U NP Sum between the minocycline and placebo groups are the same. The sample size calculation showed that 100 (50 participants in each group) were required to detect the clinically meaningful difference of 0.5 with 85% power, 0.05 Type I error, twosample and twosided test. 

[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue was not adjusted for multiple comparisons.  
[5]  Other relevant estimation information: 
No text entered. 
2. Secondary:  24week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage [ Time Frame: At baseline and week 24 ] 
Measure Type  Secondary 

Measure Title  24week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage 
Measure Description  The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The descriptive statistics were based on observed data. Since all participants reported there were no change in the MSK score at week 24, no statistical test was conducted. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
28  27 
24week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage [Units: Participants] 

No Change/Worse  28  27 
Better  0  0 
No statistical analysis provided for 24week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage
3. Secondary:  24week Change of Karnofsky Performance Score [ Time Frame: At baseline and week 24 ] 
Measure Type  Secondary 

Measure Title  24week Change of Karnofsky Performance Score 
Measure Description  The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

This analysis includes the participants with Karnofsky performance score at baseline and week 24. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
32  31 
24week Change of Karnofsky Performance Score [Units: Percentage of participants] 

No Change/Worse  97  94 
Better  3  6 
Statistical Analysis 1 for 24week Change of Karnofsky Performance Score
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Fisher Exact 
P Value ^{[4]}  0.613 
Median Difference (Net) ^{[5]}  0.053 
95% Confidence Interval  0.043 to 0.062 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the percentage of participants feeling "better" in the minocycline group after 24 week treatment is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons.  
[5]  Other relevant estimation information: 
No text entered. 
4. Secondary:  Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. [ Time Frame: Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 ] 
Measure Type  Secondary 

Measure Title  Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. 
Measure Description  The outcome is the time to first Grade ≥ 2 toxicity and/or sign and symptoms from study treatment initiation up to week 24. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, lifethreatening, or death event. 
Time Frame  Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

This analysis includes every randomized participants. A total of 21 minocycline and 20 placebo participants reported at least one Grade ≥ 2 toxicity and/or sign and symptoms during 24 weeks 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
36  37 
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. [Units: Participants with an event] 

04 weeks  12  10 
4.01  12 weeks  6  7 
12.01  24 weeks  3  3 
Statistical Analysis 1 for Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Log Rank 
P Value ^{[4]}  0.661 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the survival curve for the first Grade ≥ 2 toxicity and/or sign and symptoms in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons. 
5. Secondary:  Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms [ Time Frame: Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks ] 
Measure Type  Secondary 

Measure Title  Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms 
Measure Description  The outcome is the time of first Grade ≥ 2 toxicity and/or sign and symptoms from treatment initiation up to 48 weeks. The grade was determined by clinicians and an Grade ≥ 2 event means moderate, severe, lifethreatening, or death event. 
Time Frame  Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

This analysis includes every randomized participants. A total of 22 minocycline and 21 placebo participants reported at least one Grade ≥ 2 toxicity and/or sign and symptoms during 48 weeks. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
36  37 
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms [Units: Participants with an event] 

04 weeks  12  10 
4.0112 weeks  6  7 
12.0124 weeks  3  3 
24.0148 weeks  1  1 
Statistical Analysis 1 for Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Log Rank 
P Value ^{[4]}  0.941 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the 48week survival curve for the first Grade ≥ 2 toxicity and/or sign and symptoms in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
No text entered.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons. 
6. Secondary:  24week Change of CD4 Cell Counts [ Time Frame: At baseline and week 24 ] 
Measure Type  Secondary 

Measure Title  24week Change of CD4 Cell Counts 
Measure Description  The outcome is defined as CD4 cell count at week 24  CD4 cell count at baseline. The unit is cells/mm^3. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

This analysis used the participants with CD4 cell counts at baseline and week 24. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
29  28 
24week Change of CD4 Cell Counts [Units: Cells/mm^3] Mean (Standard Deviation) 
25.28 (70.85)  28.57 (61.65) 
Statistical Analysis 1 for 24week Change of CD4 Cell Counts
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Regression, Linear 
P Value ^{[4]}  0.647 
Mean Difference (Net) ^{[5]}  8.11 
95% Confidence Interval  27.23 to 43.45 
Standard Error of the mean  (17.63) 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the mean 24week change of CD4 cell counts in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
The model was adjusted for the baseline CD4 counts.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons.  
[5]  Other relevant estimation information: 
No text entered. 
7. Secondary:  48week Change of CD4 Cell Counts [ Time Frame: At baseline and week 48 ] 
Measure Type  Secondary 

Measure Title  48week Change of CD4 Cell Counts 
Measure Description  The outcome is defined as CD4 cell count at week 48  CD4 cell count at baseline. The unit is cells/mm^3. 
Time Frame  At baseline and week 48 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

This analysis used the participants with CD4 cell counts at baseline and week 48. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
13  16 
48week Change of CD4 Cell Counts [Units: Cells/mm^3] Mean (Standard Deviation) 
61.15 (80.46)  56.50 (84.97) 
Statistical Analysis 1 for 48week Change of CD4 Cell Counts
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Regression, Linear 
P Value ^{[4]}  0.813 
Mean Difference (Net) ^{[5]}  7.77 
95% Confidence Interval  59.07 to 74.60 
Standard Error of the mean  (32.51) 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the mean 48week change in CD4 cell counts in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
The model was adjusted for the baseline CD4 counts.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue was not adjusted for multiple comparisons.  
[5]  Other relevant estimation information: 
No text entered. 
8. Secondary:  24week Change of Instrumental Activities of Daily Living [ Time Frame: At baseline and week 24 ] 
Measure Type  Secondary 

Measure Title  24week Change of Instrumental Activities of Daily Living 
Measure Description  The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The analysis includes participants with IADL scores at baseline and week 24. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
28  26 
24week Change of Instrumental Activities of Daily Living [Units: Percentage of participants] 

No Change/Worse  86  88 
Better  14  12 
Statistical Analysis 1 for 24week Change of Instrumental Activities of Daily Living
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Regression, Logistic 
P Value ^{[4]}  0.764 
Odds Ratio (OR) ^{[5]}  1.28 
95% Confidence Interval  0.26 to 6.34 
Standard Error of the mean  (0.82) 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the percentage of being "better" at week 24 compared to baseline in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
The model was not adjusted for any covariate (due to small number of being "better" in both groups.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons.  
[5]  Other relevant estimation information: 
No text entered. 
9. Secondary:  24week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) [ Time Frame: At baseline and week 24 ] 
Measure Type  Secondary 

Measure Title  24week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) 
Measure Description  The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24  the viral loads (Log10 transformed) at baseline. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The analysis includes participants with HIV RNA viral loads at baseline and week 24. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
22  25 
24week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) [Units: copies/mL] Median (InterQuartile Range) 
0.22 (0.14 to 0.50) 
0.13 (0.23 to 0.43) 
Statistical Analysis 1 for 24week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  KruskalWallis 
P Value ^{[4]}  0.766 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the median log10transformed HIV RNA viral loads in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
The chisquare score was 0.024 and the degree of freedom was 1.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons. 
10. Secondary:  24week Change of Center for Epidemiologic Studies Depression (CESD) Score [ Time Frame: At baseline and week 24 ] 
Measure Type  Secondary 

Measure Title  24week Change of Center for Epidemiologic Studies Depression (CESD) Score 
Measure Description 
The outcome is the total CESD score at week 24  the total CESD score at baseline. The total CESD score is based on 20 CESD items, such as "I was bothered by things that usually don't bother me" and "I did not feel like eating, my appetite was poor". Patients were asked to answer each item by 4 scales: (1) Rarely, (2) Sometimes, (3) Occasionally, and (4) Most of the time. After 4 negative items were multiplied by 1, the total CESD score is a simple sum of all items. The min and Max are 0 and 60, respectively. Higher scores indicate more severe depressive symptoms. 
Time Frame  At baseline and week 24 
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate. 

The analysis includes participants with CESD scores at baseline and week 24. 
Reporting Groups
Description  

Minocycline  Minocycline 100 mg orally every 12 hours 
Placebo  Placebo minocycline capsules every 12 hours 
Measured Values
Minocycline  Placebo  

Participants Analyzed [Units: Participants] 
31  28 
24week Change of Center for Epidemiologic Studies Depression (CESD) Score [Units: Scores on a scale] Mean (Standard Deviation) 
4.19 (10.86)  4.04 (8.27) 
Statistical Analysis 1 for 24week Change of Center for Epidemiologic Studies Depression (CESD) Score
Groups ^{[1]}  All groups 

Statistical Test Type ^{[2]}  Superiority or Other 
Statistical Method ^{[3]}  Regression, Linear 
P Value ^{[4]}  0.915 
Mean Difference (Net) ^{[5]}  0.19 
95% Confidence Interval  3.40 to 3.78 
Standard Error of the mean  (1.79) 
[1]  Additional details about the analysis, such as null hypothesis and power calculation: 

The null hypothesis is that the mean 24week change of CESD score in the minocycline group is the same as the one in the placebo group.  
[2]  Details of power calculation, definition of noninferiority margin, and other key parameters: 
No text entered.  
[3]  Other relevant method information, such as adjustments or degrees of freedom: 
The model was adjusted for the baseline CESD and MSK scores.  
[4]  Additional information, such as whether or not the pvalue is adjusted for multiple comparisons and the a priori threshold for statistical significance: 
The pvalue is not adjusted for multiple comparisons.  
[5]  Other relevant estimation information: 
No text entered. 
Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data 

The estimated sample size was 100; however, due to early termination of the study, the total number of randomized participants was 73. 
More Information
Principal Investigators are NOT employed by the organization sponsoring the study. 
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. 
Results Point of Contact:
Organization: Harvard School of Public Health
phone: 6174322837
email: miyahara@sdac.harvard.edu
Responsible Party:  Ned Sacktor, MD, Johns Hopkins School of Medicine 
ClinicalTrials.gov Identifier:  NCT00855062 History of Changes 
Other Study ID Numbers: 
Uganda minocycline study Grant Number: 5 UO1 NS32228 
First Submitted:  March 2, 2009 
First Posted:  March 3, 2009 
Results First Submitted:  December 17, 2010 
Results First Posted:  February 25, 2011 
Last Update Posted:  February 25, 2011 