Minocycline for HIV+ Cognitive Impairment in Uganda
Study Details
Study Description
Brief Summary
Purpose: The purpose of the study is to assess the safety and effectiveness of minocycline, an antibiotic, in the treatment of Human immunodeficiency virus (HIV)-associated cognitive impairment in Uganda.
Study Design: Treatment, 24-week Randomized, Placebo-Controlled, Double-Blind Phase with Optional 24-week Open Label Phase for Subjects with a cluster of differentiation 4 (CD4) Count in the 251-350 Range
-
Arm 1: Minocycline 100 mg orally every 12 hours (50 subjects)
-
Arm 2: Matching placebo orally every 12 hours (50 subjects)
Primary Objective:
· To examine whether minocycline treatment will improve cognitive performance after 24 weeks compared to baseline
Secondary Objectives:
-
To examine whether minocycline treatment for 24 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment
-
To examine whether minocycline treatment for 48 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment
-
To examine whether minocycline treatment for 24 weeks improves functional impairment
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1/Phase 2 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Active Comparator: Minocycline Minocycline 100 mg orally every 12 hours |
Drug: minocycline
100 mg capsule every 12 hours by mouth
|
Placebo Comparator: Placebo Placebo minocycline capsules every 12 hours |
Drug: minocycline placebo capsule
1 capsule every 12 hours by mouth
|
Outcome Measures
Primary Outcome Measures
- 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) [At baseline and week 24]
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.
Secondary Outcome Measures
- 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage [At baseline and week 24]
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
- 24-week Change of Karnofsky Performance Score [At baseline and week 24]
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
- Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. [Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24]
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 From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms [Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks]
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.
- 24-week Change of CD4 Cell Counts [At baseline and week 24]
The outcome is defined as CD4 cell count at week 24 - CD4 cell count at baseline. The unit is cells/mm^3.
- 48-week Change of CD4 Cell Counts [At baseline and week 48]
The outcome is defined as CD4 cell count at week 48 - CD4 cell count at baseline. The unit is cells/mm^3.
- 24-week Change of Instrumental Activities of Daily Living [At baseline and week 24]
The outcome is a new dichotomous variable: no change/worse vs. better at 24 weeks compared to baseline.
- 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) [At baseline and week 24]
The outcome is the HIV RNA plasma viral loads (Log10 transformed) at week 24 - the viral loads (Log10 transformed) at baseline.
- 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score [At baseline and week 24]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
HIV infection prior to study entry
-
Naïve to any antiretroviral regimen and ineligible to receive antiretroviral therapy by cluster of differentiation 4 (CD4) criteria in Uganda
-
Negative serum or urine pregnancy test for women of childbearing potential
-
Willingness to use birth control
-
Age 18-65 years
-
AIDS Dementia Scale Stage 0.5 OR 1
-
Impaired cognitive performance as evidenced by an International HIV Dementia Scale (HDS) as defined by the protocol
-
Ability to sit or stand and swallow intact capsules with an 8-ounce glass of water
-
Ability and willingness of subject or legal guardian/ representative to give written informed consent
-
Resident within a 20km radius of Kampala city
Exclusion Criteria:
-
Current cancers other than basal cell carcinoma, in situ carcinoma of the cervix, or Kaposi's sarcoma without evidence of visceral involvement or which does not require systemic chemotherapy
-
Severe premorbid psychiatric illness, including schizophrenia and major depression which, in the in investigator's opinion, is likely to interfere with study compliance
-
Active symptomatic AIDS-defining opportunistic infection within 45 days prior to study entry
-
Confounding neurological disorders as defined in the protocol
-
Central nervous system infections or cancers as defined in the protocol
-
Systemic lupus
-
Thyroid disease diagnosed within 24 weeks prior to entry
-
Breastfeeding
-
Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
-
Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the investigator
-
History of allergy/sensitivity to minocycline or other tetracyclines and their formulations
-
Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the subject's ability to participate in the study. This includes an individual found to have an HIV dementia scale stage 3 or 4.
-
Any esophageal or other condition that would interfere with the swallowing of the study medication
-
Use of excluded drugs as defined by the protocol
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Infecious Diseas Institute | Kampala | Uganda |
Sponsors and Collaborators
- Johns Hopkins University
- Makerere University
Investigators
- Principal Investigator: Ned Sacktor, MD, Johns Hopkins School of Medicine
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- Uganda minocycline study
- Grant Number: 5 UO1 NS32228
Study Results
Participant Flow
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 Detail | 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 |
---|---|---|
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 |
Period Title: Step1 | ||
STARTED | 19 | 21 |
COMPLETED | 13 | 15 |
NOT COMPLETED | 6 | 6 |
Baseline Characteristics
Arm/Group Title | Minocycline | Placebo | Total |
---|---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours | Total of all reporting groups |
Overall Participants | 36 | 37 | 73 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
36
100%
|
37
100%
|
73
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
37.3
(8.21)
|
36.7
(7.17)
|
37.0
(7.66)
|
Sex: Female, Male (Count of Participants) | |||
Female |
34
94.4%
|
32
86.5%
|
66
90.4%
|
Male |
2
5.6%
|
5
13.5%
|
7
9.6%
|
Region of Enrollment (participants) [Number] | |||
Uganda |
36
100%
|
37
100%
|
73
100%
|
Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale (Number) [Number] | |||
Equivocal/subclinical |
35
97.2%
|
37
100%
|
72
98.6%
|
Mild |
1
2.8%
|
0
0%
|
1
1.4%
|
Baseline Cluster of Differentiation Four (CD4) Count (cells/mm^3) [Median (Full Range) ] | |||
Median (Full Range) [cells/mm^3] |
319
|
305
|
313
|
Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL)) (copies/mL) [Log Mean (Inter-Quartile Range) ] | |||
Log Mean (Inter-Quartile Range) [copies/mL] |
4.41
|
4.59
|
4.50
|
Baseline Karnofsky's Performance Score (Number) [Number] | |||
80 (Karnofsky Score) |
1
2.8%
|
2
5.4%
|
3
4.1%
|
90 (Karnofsky Score) |
35
97.2%
|
34
91.9%
|
69
94.5%
|
100 (Karnofsky Score) |
0
0%
|
1
2.7%
|
1
1.4%
|
Baseline Instrumental Activities of Daily Living (IADL) (Number) [Number] | |||
Primarily cognitive problems |
1
2.8%
|
0
0%
|
1
1.4%
|
Primarily physical problems |
6
16.7%
|
2
5.4%
|
8
11%
|
Not having any difficulties on the tasks |
29
80.6%
|
35
94.6%
|
64
87.7%
|
Baseline Overall Neurological Assessment (Number) [Number] | |||
Normal neurological assessment |
26
72.2%
|
30
81.1%
|
56
76.7%
|
Central Nervous System (CNS) abnormality only |
4
11.1%
|
5
13.5%
|
9
12.3%
|
Peripheral Nervous System (PNS) abnormality only |
4
11.1%
|
1
2.7%
|
5
6.8%
|
CNS and PNS abnormality |
1
2.8%
|
1
2.7%
|
2
2.7%
|
Can not assess |
1
2.8%
|
0
0%
|
1
1.4%
|
Baseline Uganda Neuropsychological Test Battery Summary measure (U NP Sum) (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-0.97
(0.78)
|
-0.97
(0.86)
|
-0.97
(0.82)
|
WHO-UCLA Auditory Verbal Learning Test (AVLT): Trials Total (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-1.28
(0.88)
|
-1.48
(1.14)
|
-1.38
(1.02)
|
WHO-UCLA Auditory Verbal Learning Test (AVLT): Delayed (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-1.17
(0.79)
|
-1.15
(1.18)
|
-1.16
(1.00)
|
Color Trails 1 (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-1.35
(2.03)
|
-1.65
(3.03)
|
-1.51
(2.60)
|
Color Trails 2 (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-2.55
(2.07)
|
-2.33
(2.05)
|
-2.44
(2.05)
|
Grooved Pegboard Dominant (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-0.34
(1.58)
|
-0.03
(1.14)
|
-0.18
(1.37)
|
Grooved Pegboard Non-dominant (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-0.56
(1.82)
|
-0.48
(1.42)
|
-0.52
(1.61)
|
Symbol Digit (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-0.87
(0.96)
|
-0.86
(0.80)
|
-0.86
(0.88)
|
Digit Span Backward (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
-0.68
(0.75)
|
-0.94
(1.06)
|
-0.81
(0.93)
|
Digit Span Forward (z-scores) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [z-scores] |
0.02
(0.79)
|
0.19
(0.99)
|
0.11
(0.90)
|
Outcome Measures
Title | 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 30 | 29 |
Mean (Standard Deviation) [z-score] |
0.44
(0.74)
|
0.49
(0.67)
|
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 | ||
Statistical Test of Hypothesis | p-Value | 0.370 |
Comments | The p-value was not adjusted for multiple comparisons. | |
Method | Regression, Linear | |
Comments | ||
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 |
Title | 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 28 | 27 |
No Change/Worse |
28
77.8%
|
27
73%
|
Better |
0
0%
|
0
0%
|
Title | 24-week Change of Karnofsky Performance Score |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
This analysis includes the participants with Karnofsky performance score at baseline and week 24. |
Arm/Group Title | Minocycline | Placebo |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 32 | 31 |
No Change/Worse |
97
269.4%
|
94
254.1%
|
Better |
3
8.3%
|
6
16.2%
|
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 | ||
Statistical Test of Hypothesis | p-Value | 0.613 |
Comments | The p-value is not adjusted for multiple comparisons. | |
Method | Fisher Exact | |
Comments | ||
Method of Estimation | Estimation Parameter | Median Difference (Net) |
Estimated Value | 0.053 | |
Confidence Interval |
(2-Sided) 95% 0.043 to 0.062 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms. |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 36 | 37 |
0-4 weeks |
12
33.3%
|
10
27%
|
4.01 - 12 weeks |
6
16.7%
|
7
18.9%
|
12.01 - 24 weeks |
3
8.3%
|
3
8.1%
|
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 | ||
Statistical Test of Hypothesis | p-Value | 0.661 |
Comments | The p-value is not adjusted for multiple comparisons. | |
Method | Log Rank | |
Comments |
Title | Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms |
---|---|
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 |
Outcome Measure Data
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 |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 36 | 37 |
0-4 weeks |
12
33.3%
|
10
27%
|
4.01-12 weeks |
6
16.7%
|
7
18.9%
|
12.01-24 weeks |
3
8.3%
|
3
8.1%
|
24.01-48 weeks |
1
2.8%
|
1
2.7%
|
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 | ||
Statistical Test of Hypothesis | p-Value | 0.941 |
Comments | The p-value is not adjusted for multiple comparisons. | |
Method | Log Rank | |
Comments |
Title | 24-week Change of CD4 Cell Counts |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
This analysis used the participants with CD4 cell counts at baseline and week 24. |
Arm/Group Title | Minocycline | Placebo |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 29 | 28 |
Mean (Standard Deviation) [cells/mm^3] |
-25.28
(70.85)
|
-28.57
(61.65)
|
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 | ||
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 |
Title | 48-week Change of CD4 Cell Counts |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
This analysis used the participants with CD4 cell counts at baseline and week 48. |
Arm/Group Title | Minocycline | Placebo |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 13 | 16 |
Mean (Standard Deviation) [cells/mm^3] |
-61.15
(80.46)
|
-56.50
(84.97)
|
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 | ||
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 |
Title | 24-week Change of Instrumental Activities of Daily Living |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
The analysis includes participants with IADL scores at baseline and week 24. |
Arm/Group Title | Minocycline | Placebo |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 28 | 26 |
No Change/Worse |
86
238.9%
|
88
237.8%
|
Better |
14
38.9%
|
12
32.4%
|
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 | ||
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 |
Title | 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed) |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
The analysis includes participants with HIV RNA viral loads at baseline and week 24. |
Arm/Group Title | Minocycline | Placebo |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 22 | 25 |
Median (Inter-Quartile Range) [copies/mL] |
0.22
|
0.13
|
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 | ||
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. |
Title | 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score |
---|---|
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 |
Outcome Measure Data
Analysis Population Description |
---|
The analysis includes participants with CES-D scores at baseline and week 24. |
Arm/Group Title | Minocycline | Placebo |
---|---|---|
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours |
Measure Participants | 31 | 28 |
Mean (Standard Deviation) [scores on a scale] |
-4.19
(10.86)
|
-4.04
(8.27)
|
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 | ||
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 |
Adverse Events
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 | ||
Arm/Group Description | Minocycline 100 mg orally every 12 hours | Placebo minocycline capsules every 12 hours | ||
All Cause Mortality |
||||
Minocycline | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
Minocycline | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/36 (5.6%) | 1/37 (2.7%) | ||
Hepatobiliary disorders | ||||
Sgpt | 0/36 (0%) | 0 | 1/37 (2.7%) | 1 |
Sgot | 0/36 (0%) | 0 | 1/37 (2.7%) | 1 |
Infections and infestations | ||||
Death | 1/36 (2.8%) | 1 | 0/37 (0%) | 0 |
Renal and urinary disorders | ||||
Potassium | 1/36 (2.8%) | 1 | 0/37 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
Minocycline | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 26/36 (72.2%) | 25/37 (67.6%) | ||
Blood and lymphatic system disorders | ||||
Absolute Neutrophil Count | 12/36 (33.3%) | 21 | 12/37 (32.4%) | 12 |
White Blood Cells | 0/36 (0%) | 0 | 2/37 (5.4%) | 2 |
General disorders | ||||
Fever | 2/36 (5.6%) | 2 | 1/37 (2.7%) | 1 |
Carbon Dioxide | 4/36 (11.1%) | 4 | 2/37 (5.4%) | 2 |
Hepatobiliary disorders | ||||
SGOT | 3/36 (8.3%) | 3 | 0/37 (0%) | 0 |
Renal and urinary disorders | ||||
Phosphorus | 3/36 (8.3%) | 3 | 3/37 (8.1%) | 3 |
Sodium | 2/36 (5.6%) | 2 | 1/37 (2.7%) | 1 |
Skin and subcutaneous tissue disorders | ||||
Allergic Rash | 0/36 (0%) | 0 | 4/37 (10.8%) | 4 |
Limitations/Caveats
More Information
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 |
miyahara@sdac.harvard.edu |
- Uganda minocycline study
- Grant Number: 5 UO1 NS32228