Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Minocycline for HIV+ Cognitive Impairment in Uganda

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00855062
Recruitment Status : Terminated (The Neurologic AIDS Research Consortium Data Safety and Monitoring Board committee recommended to terminate the study early due to futility on 11/6/2009.)
First Posted : March 3, 2009
Results First Posted : February 25, 2011
Last Update Posted : February 25, 2011
Sponsor:
Collaborator:
Makerere University
Information provided by:
Johns Hopkins University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Single Group Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions HIV-associated Cognitive Impairment
HIV Infections
Interventions Drug: minocycline
Drug: minocycline placebo capsule
Enrollment 73
Recruitment Details 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.
Pre-assignment Details 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".
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description Minocycline 100 mg orally every 12 hours Placebo minocycline capsules every 12 hours
Period Title: Step1
Started 36 37
Completed 26 26
Not Completed 10 11
Reason Not Completed
Early Study Closure             5             7
Adverse Event             1             1
Protocol Violation             1             0
Pregnancy             1             0
Withdrawal by Subject             2             3
Period Title: Step2
Started 19 [1] 21 [2]
Completed 13 15
Not Completed 6 6
Reason Not Completed
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.
Arm/Group Title Minocycline Placebo Total
Hide Arm/Group Description Minocycline 100 mg orally every 12 hours Placebo minocycline capsules every 12 hours Total of all reporting groups
Overall Number of Baseline Participants 36 37 73
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 73 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
36
 100.0%
37
 100.0%
73
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 37 participants 73 participants
37.3  (8.21) 36.7  (7.17) 37.0  (7.66)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 73 participants
Female
34
  94.4%
32
  86.5%
66
  90.4%
Male
2
   5.6%
5
  13.5%
7
   9.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Uganda Number Analyzed 36 participants 37 participants 73 participants
36 37 73
Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 73 participants
Equivocal/subclinical 35 37 72
Mild 1 0 1
[1]
Measure Description:

The Memorial Sloan Kettering (MSK) clinical scale was defined below:

  • Stage 0: normal
  • Stage 0.5: equivocal/subclinical
  • Stage 1: mild
  • Stage 2: moderate
  • Stage 3: severe
  • Stage 4: end stage
Baseline Cluster of Differentiation Four (CD4) Count  
Median (Full Range)
Unit of measure:  Cells/mm^3
Number Analyzed 36 participants 37 participants 73 participants
319
(251 to 469)
305
(252 to 500)
313
(251 to 500)
Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL))  
Log Mean (Inter-Quartile Range)
Unit of measure:  copies/mL
Number Analyzed 36 participants 37 participants 73 participants
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] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 73 participants
80 (Karnofsky Score) 1 2 3
90 (Karnofsky Score) 35 34 69
100 (Karnofsky Score) 0 1 1
[1]
Measure Description: 100:Normal,90:normal;Minor Signs or Symptoms of Disease,80:Normal Activity with Effort;Some Signs or Symptoms of Disease,70:Cares for Self,Unable to Carry on Normal Activity or to Do Active Work,60:Requires Occasional Assistance but is Able to Care for Most of Needs,50:Requires Considerable Assistance and Frequent Medical Care,40:Disabled,Requires Special Care and Assistance,30:Severely Disabled; Hospitalization Indicated Although Death is Not Imminent,20:Very Sick; Hospitalization Necessary;Active Supportive Treatment is Necessary,10:Moribund, Fatal Processes Progressing Rapidly,0:Death
Baseline Instrumental Activities of Daily Living (IADL)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 73 participants
Primarily cognitive problems 1 0 1
Primarily physical problems 6 2 8
Not having any difficulties on the tasks 29 35 64
[1]
Measure Description:

16 tasks: Housekeeping,Managing Finances,Buying Groceries,Cooking,Planning Social Activities,Understanding Reading Materials/TV,Transportation,Using the Telephone,Home Repairs,Bathing,Dressing,Shopping,Laundry,Taking/Keeping Track of Medication,Child Care,Work.

For the baseline IADL measure, participants were given four choices to choose for having difficulty on the 16 tasks:Primarily Cognitive problems,Primarily physical problems,equally cognitive and physical problems,not having any difficulties on previous tasks.

Baseline Overall Neurological Assessment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 37 participants 73 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] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-0.97  (0.78) -0.97  (0.86) -0.97  (0.82)
[1]
Measure Description: Uganda Neuropsychological Test Battery Summary measure (U NP Sum)is the average z-scores of the 9 neurupsychological tests:Grooved Pegboard Dominant Hand,Grooved Pegboard Non-dominant Hand,Color Trail1,Color Trail2,Symbol Digit,WHO/UCLA Verbal Learning Test Trial 5,WHO/UCLA Verbal Learning Test Delayed Recall,Digit Span-Forward,Digit Span-Backward Since the score depends on age and education levels, the raw score was standardized as follows: Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.
WHO-UCLA Auditory Verbal Learning Test (AVLT): Trials Total   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-1.28  (0.88) -1.48  (1.14) -1.38  (1.02)
[1]
Measure Description:

World Health Organization-University of California Los Angeles (WHO-UCLA) Auditory Verbal Learning Test (AVLT) is a full-scale memory assessment.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

WHO-UCLA Auditory Verbal Learning Test (AVLT): Delayed   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-1.17  (0.79) -1.15  (1.18) -1.16  (1.00)
[1]
Measure Description:

World Health Organization-University of California Los Angeles (WHO-UCLA) Auditory Verbal Learning Test (AVLT) is a memory assessment.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Color Trails 1   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-1.35  (2.03) -1.65  (3.03) -1.51  (2.60)
[1]
Measure Description:

The Color Trails tests measure speed of attention, sequencing, mental flexibility, visual search, and motor function.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Color Trails 2   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-2.55  (2.07) -2.33  (2.05) -2.44  (2.05)
[1]
Measure Description:

The Color Trails tests measure speed of attention, sequencing, mental flexibility, visual search, and motor function.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Grooved Pegboard Dominant   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-0.34  (1.58) -0.03  (1.14) -0.18  (1.37)
[1]
Measure Description:

The grooved pegboard is a manipulative dexterity test requiring rapid visual-motor coordination. The test is completed using the dominant hand (GPD) and then using the non-dominant hand (GPN). The score for each hand is the time in seconds that the participant takes to complete the entire board.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Grooved Pegboard Non-dominant   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-0.56  (1.82) -0.48  (1.42) -0.52  (1.61)
[1]
Measure Description:

The grooved pegboard is a manipulative dexterity test requiring rapid visual-motor coordination. The test is completed using the dominant hand (GPD) and then using the non-dominant hand (GPN). The score for each hand is the time in seconds that the participant takes to complete the entire board.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Symbol Digit   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-0.87  (0.96) -0.86  (0.80) -0.86  (0.88)
[1]
Measure Description:

This test assesses the participant's ability to maintain rapid visual-motor sequencing in a timed test. The score is the total number of correctly transcribed numbers in the time limit (90 seconds). Participants receive 1 point for each item filled in correctly. Maximum score is 110 points.

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Digit Span Backward   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
-0.68  (0.75) -0.94  (1.06) -0.81  (0.93)
[1]
Measure Description:

Digit span assesses attention, concentration, and mental control(e.g., Repeat the numbers 1-2-3 in reverse sequence).

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

Digit Span Forward   [1] 
Mean (Standard Deviation)
Unit of measure:  Z-scores
Number Analyzed 36 participants 37 participants 73 participants
0.02  (0.79) 0.19  (0.99) 0.11  (0.90)
[1]
Measure Description:

Digit span assesses attention, concentration, and mental control(e.g., Repeat the numbers 1-2-3 in reverse sequence).

Since the score depends on age and education levels, the raw score was standardized as follows:

Zx =(x − μx)/σx where Zx is the age and education adjusted z-score, x is the raw score, and μx and σx are the age and education stratified norms.

1.Primary Outcome
Title 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
Hide 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 norm-adjusted ("z") scores for Grooved Pegboard Dominant Hand, Grooved Pegboard Non-dominant Hand, Color Trails 1, Color Trails 2, Symbol Digit, WHO-UCLA Verbal Learning test Trial 5, WHO-UCLA 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
Hide Outcome Measure Data
Hide Analysis Population Description
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).
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 30 29
Mean (Standard Deviation)
Unit of Measure: z-score
0.44  (0.74) 0.49  (0.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments

The null hypothesis was that the 24-week 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, two-sample and two-sided test.

Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.370
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments [Not Specified]
Method of Estimation Estimation Parameter Slope
Estimated Value -0.026
Confidence Interval (2-Sided) 95%
-0.512 to 0.460
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.248
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 28 27
Measure Type: Number
Unit of Measure: participants
No Change/Worse 28 27
Better 0 0
3.Secondary Outcome
Title 24-week Change of Karnofsky Performance Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis includes the participants with Karnofsky performance score at baseline and week 24.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 32 31
Measure Type: Number
Unit of Measure: percentage of participants
No Change/Worse 97 94
Better 3 6
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.613
Comments The p-value is not adjusted for multiple comparisons.
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Median Difference (Net)
Estimated Value 0.053
Confidence Interval (2-Sided) 95%
0.043 to 0.062
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.
Hide 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, life-threatening, or death event.
Time Frame Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 36 37
Measure Type: Number
Unit of Measure: participants with an event
0-4 weeks 12 10
4.01 - 12 weeks 6 7
12.01 - 24 weeks 3 3
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.661
Comments The p-value is not adjusted for multiple comparisons.
Method Log Rank
Comments [Not Specified]
5.Secondary Outcome
Title Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms
Hide 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, life-threatening, or death event.
Time Frame Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 36 37
Measure Type: Number
Unit of Measure: participants with an event
0-4 weeks 12 10
4.01-12 weeks 6 7
12.01-24 weeks 3 3
24.01-48 weeks 1 1
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments The null hypothesis is that the 48-week 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.941
Comments The p-value is not adjusted for multiple comparisons.
Method Log Rank
Comments [Not Specified]
6.Secondary Outcome
Title 24-week Change of CD4 Cell Counts
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis used the participants with CD4 cell counts at baseline and week 24.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 29 28
Mean (Standard Deviation)
Unit of Measure: cells/mm^3
-25.28  (70.85) -28.57  (61.65)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments The null hypothesis is that the mean 24-week change of CD4 cell counts in the minocycline group is the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.647
Comments The p-value is not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the baseline CD4 counts.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.11
Confidence Interval (2-Sided) 95%
-27.23 to 43.45
Parameter Dispersion
Type: Standard Error of the mean
Value: 17.63
Estimation Comments [Not Specified]
7.Secondary Outcome
Title 48-week Change of CD4 Cell Counts
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
This analysis used the participants with CD4 cell counts at baseline and week 48.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 13 16
Mean (Standard Deviation)
Unit of Measure: cells/mm^3
-61.15  (80.46) -56.50  (84.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments The null hypothesis is that the mean 48-week change in CD4 cell counts in the minocycline group is the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.813
Comments The p-value was not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the baseline CD4 counts.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 7.77
Confidence Interval (2-Sided) 95%
-59.07 to 74.60
Parameter Dispersion
Type: Standard Error of the mean
Value: 32.51
Estimation Comments [Not Specified]
8.Secondary Outcome
Title 24-week Change of Instrumental Activities of Daily Living
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes participants with IADL scores at baseline and week 24.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 28 26
Measure Type: Number
Unit of Measure: percentage of participants
No Change/Worse 86 88
Better 14 12
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.764
Comments The p-value is not adjusted for multiple comparisons.
Method Regression, Logistic
Comments The model was not adjusted for any covariate (due to small number of being "better" in both groups.
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.28
Confidence Interval 95%
0.26 to 6.34
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.82
Estimation Comments [Not Specified]
9.Secondary Outcome
Title 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes participants with HIV RNA viral loads at baseline and week 24.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 22 25
Median (Inter-Quartile Range)
Unit of Measure: copies/mL
0.22
(-0.14 to 0.50)
0.13
(-0.23 to 0.43)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments The null hypothesis is that the median log10-transformed HIV RNA viral loads in the minocycline group is the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.766
Comments The p-value is not adjusted for multiple comparisons.
Method Kruskal-Wallis
Comments The chi-square score was 0.024 and the degree of freedom was 1.
10.Secondary Outcome
Title 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score
Hide Description

The outcome is the total CES-D score at week 24 - the total CES-D score at baseline.

The total CES-D score is based on 20 CES-D 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 CES-D 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
Hide Outcome Measure Data
Hide Analysis Population Description
The analysis includes participants with CES-D scores at baseline and week 24.
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description:
Minocycline 100 mg orally every 12 hours
Placebo minocycline capsules every 12 hours
Overall Number of Participants Analyzed 31 28
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-4.19  (10.86) -4.04  (8.27)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Minocycline, Placebo
Comments The null hypothesis is that the mean 24-week change of CES-D score in the minocycline group is the same as the one in the placebo group.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.915
Comments The p-value is not adjusted for multiple comparisons.
Method Regression, Linear
Comments The model was adjusted for the baseline CES-D and MSK scores.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
-3.40 to 3.78
Parameter Dispersion
Type: Standard Error of the mean
Value: 1.79
Estimation Comments [Not Specified]
Time Frame 48 weeks
Adverse Event Reporting Description The lab assessments were conducted at weeks 0, 12, 24, and 48.
 
Arm/Group Title Minocycline Placebo
Hide Arm/Group Description Minocycline 100 mg orally every 12 hours Placebo minocycline capsules every 12 hours
All-Cause Mortality
Minocycline Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Minocycline Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/36 (5.56%)      1/37 (2.70%)    
Hepatobiliary disorders     
Sgpt  1 [1]  0/36 (0.00%)  0 1/37 (2.70%)  1
Sgot  1 [2]  0/36 (0.00%)  0 1/37 (2.70%)  1
Infections and infestations     
Death  1 [3]  1/36 (2.78%)  1 0/37 (0.00%)  0
Renal and urinary disorders     
Potassium  1 [4]  1/36 (2.78%)  1 0/37 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, Appendix 76
[1]
The lab value was 836 when the normal value was 45.
[2]
The lab value was 901 when the normal value was 40.
[3]
The patient died due to Pulmonary Tuberculosis. The cause of death was unrelated to the study treatment as she was not on the study treatment at the time of her death.
[4]
The participant had high potassium level. The value was 7.8 when the normal limit was 5.3.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Minocycline Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   26/36 (72.22%)      25/37 (67.57%)    
Blood and lymphatic system disorders     
Absolute Neutrophil Count  1  12/36 (33.33%)  21 12/37 (32.43%)  12
White Blood Cells  1  0/36 (0.00%)  0 2/37 (5.41%)  2
General disorders     
Fever  1  2/36 (5.56%)  2 1/37 (2.70%)  1
Carbon Dioxide  1  4/36 (11.11%)  4 2/37 (5.41%)  2
Hepatobiliary disorders     
SGOT  1  3/36 (8.33%)  3 0/37 (0.00%)  0
Renal and urinary disorders     
Phosphorus  1  3/36 (8.33%)  3 3/37 (8.11%)  3
Sodium  1  2/36 (5.56%)  2 1/37 (2.70%)  1
Skin and subcutaneous tissue disorders     
Allergic Rash  1  0/36 (0.00%)  0 4/37 (10.81%)  4
Indicates events were collected by systematic assessment
1
Term from vocabulary, Appendix 76
The estimated sample size was 100; however, due to early termination of the study, the total number of randomized participants was 73.
Certain Agreements
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
Name/Title: Sachiko Miyahara
Organization: Harvard School of Public Health
Phone: 617-432-2837
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