CClinicalTrials.gg
Sign In
TerminatedNCT00855062Updated Feb 25, 2011Results posted

Minocycline for HIV+ Cognitive Impairment in Uganda

A Phase 1/2 interventional study of minocycline and minocycline placebo capsule in HIV-associated Cognitive Impairment and HIV Infections, sponsored by Johns Hopkins University. Terminated at 1 site in Uganda. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2011-02-25.

Sponsored by Johns Hopkins University · Phase 1/2, Interventional, and Treatment

Why this study was 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.
Phase
Phase 1/2
Study type
Interventional
Enrollment
73
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study 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
02

Conditions studied

  • HIV-associated Cognitive Impairment
  • HIV Infections

Keywords

  • Human immunodeficiency virus (HIV)
  • HIV associated cognitive impairment
  • HIV dementia
  • Uganda
  • Acquired immune deficiency syndrome (AIDS)
  • Treatment Naive
03

In context

Cognitive Dysfunction

3,843 studies on the registry are indexed under Cognitive Dysfunction; 1,100 are open to participants now.

This study's enrollment of 73 is above the median of 65 across 2,808 interventional studies indexed under Cognitive Dysfunction.

Browse Cognitive Dysfunction studies →

Lead sponsor

Johns Hopkins University is the lead sponsor of 1,783 studies on the registry; 313 are open to participants now.

Of its 203 completed or terminated interventional studies of FDA-regulated products, 140 (69%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Single group
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
73 participants (actual)

Study arms

  • Active comparator
    Minocycline

    Minocycline 100 mg orally every 12 hours

    Drug: minocycline

  • Placebo comparator
    Placebo

    Placebo minocycline capsules every 12 hours

    Drug: minocycline placebo capsule

Interventions

  • Drugminocycline

    100 mg capsule every 12 hours by mouth

  • Drugminocycline placebo capsule

    1 capsule every 12 hours by mouth

06

What researchers measure

Primary outcomes

  1. 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)

    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

Secondary outcomes

  1. 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage

    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

  2. 24-week Change of Karnofsky Performance Score

    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

  3. Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.

    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

  4. Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms

    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

  5. 24-week Change of CD4 Cell Counts

    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

  6. 48-week Change of CD4 Cell Counts

    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

  7. 24-week Change of Instrumental Activities of Daily Living

    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

  8. 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)

    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

  9. 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score

    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

07

Results

Posted Feb 25, 2011
Limitations and caveats
The estimated sample size was 100; however, due to early termination of the study, the total number of randomized participants was 73.

Participant flow

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.

Step1
Participant flow — Step1
MilestoneMinocyclinePlacebo
Started3637
Completed2626
Not completed1011
Withdrew: Early study closure57
Withdrew: Adverse event11
Withdrew: Protocol violation10
Withdrew: Pregnancy10
Withdrew: Withdrawal by subject23
Step2
Participant flow — Step2
MilestoneMinocyclinePlacebo
Started1921
Completed1315
Not completed66
Withdrew: Early study closure62
Withdrew: Adverse event03
Withdrew: Initiation of antiretroviral therapy/art01

Outcome measures

Primary24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)

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
Reported as:
Mean · z-score
24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
z-scoreMinocyclinePlacebo
24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)0.44 ± 0.740.49 ± 0.67
Statistical analysis
  • Minocycline vs Placebo · Regression, Linear · p = 0.370 (The p-value was not adjusted for multiple comparisons.) · Slope: -0.026 · 95% CI -0.512 to 0.460
Secondary24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage

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
Reported as:
Number · participants
24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage
participantsMinocyclinePlacebo
No Change/Worse2827
Better00
Secondary24-week Change of Karnofsky Performance Score

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
Reported as:
Number · percentage of participants
24-week Change of Karnofsky Performance Score
percentage of participantsMinocyclinePlacebo
No Change/Worse9794
Better36
Statistical analysis
  • Minocycline vs Placebo · Fisher Exact · p = 0.613 (The p-value is not adjusted for multiple comparisons.) · Median difference (net): 0.053 · 95% CI 0.043 to 0.062
SecondaryTime From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.

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
Reported as:
Number · participants with an event
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.
participants with an eventMinocyclinePlacebo
0-4 weeks1210
4.01 - 12 weeks67
12.01 - 24 weeks33
Statistical analysis
  • Minocycline vs Placebo · Log Rank · p = 0.661 (The p-value is not adjusted for multiple comparisons.)
SecondaryTime From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms

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
Reported as:
Number · participants with an event
Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms
participants with an eventMinocyclinePlacebo
0-4 weeks1210
4.01-12 weeks67
12.01-24 weeks33
24.01-48 weeks11
Statistical analysis
  • Minocycline vs Placebo · Log Rank · p = 0.941 (The p-value is not adjusted for multiple comparisons.)
Secondary24-week Change of CD4 Cell Counts

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
Reported as:
Mean · cells/mm^3
24-week Change of CD4 Cell Counts
cells/mm^3MinocyclinePlacebo
24-week Change of CD4 Cell Counts-25.28 ± 70.85-28.57 ± 61.65
Statistical analysis
  • Minocycline vs Placebo · Regression, Linear · p = 0.647 (The p-value is not adjusted for multiple comparisons.) · Mean difference (net): 8.11 · 95% CI -27.23 to 43.45The model was adjusted for the baseline CD4 counts.
Secondary48-week Change of CD4 Cell Counts

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
Reported as:
Mean · cells/mm^3
48-week Change of CD4 Cell Counts
cells/mm^3MinocyclinePlacebo
48-week Change of CD4 Cell Counts-61.15 ± 80.46-56.50 ± 84.97
Statistical analysis
  • Minocycline vs Placebo · Regression, Linear · p = 0.813 (The p-value was not adjusted for multiple comparisons.) · Mean difference (net): 7.77 · 95% CI -59.07 to 74.60The model was adjusted for the baseline CD4 counts.
Secondary24-week Change of Instrumental Activities of Daily Living

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
Reported as:
Number · percentage of participants
24-week Change of Instrumental Activities of Daily Living
percentage of participantsMinocyclinePlacebo
No Change/Worse8688
Better1412
Statistical analysis
  • Minocycline vs Placebo · Regression, Logistic · p = 0.764 (The p-value is not adjusted for multiple comparisons.) · Odds ratio (or): 1.28 · 95% CI 0.26 to 6.34The model was not adjusted for any covariate (due to small number of being "better" in both groups.
Secondary24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)

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
Reported as:
Median · copies/mL
24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)
copies/mLMinocyclinePlacebo
24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)0.22 (-0.14 to 0.50)0.13 (-0.23 to 0.43)
Statistical analysis
  • Minocycline vs Placebo · Kruskal-Wallis · p = 0.766 (The p-value is not adjusted for multiple comparisons.)The chi-square score was 0.024 and the degree of freedom was 1.
Secondary24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score

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
Reported as:
Mean · scores on a scale
24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score
scores on a scaleMinocyclinePlacebo
24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score-4.19 ± 10.86-4.04 ± 8.27
Statistical analysis
  • Minocycline vs Placebo · Regression, Linear · p = 0.915 (The p-value is not adjusted for multiple comparisons.) · Mean difference (net): 0.19 · 95% CI -3.40 to 3.78The model was adjusted for the baseline CES-D and MSK scores.

Adverse events

Collected over 48 weeks. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Minocycline—2/36 (5.6%)26/36 (72.2%)
Placebo—1/37 (2.7%)25/37 (67.6%)
Most frequent serious events
Most frequent serious events
EventMinocyclinePlacebo
DeathInfections and infestations1/360/37
PotassiumRenal and urinary disorders1/360/37
SgptHepatobiliary disorders0/361/37
SgotHepatobiliary disorders0/361/37
Most frequent other events
Most frequent other events
EventMinocyclinePlacebo
Absolute Neutrophil CountBlood and lymphatic system disorders12/3612/37
Carbon DioxideGeneral disorders4/362/37
Allergic RashSkin and subcutaneous tissue disorders0/364/37
PhosphorusRenal and urinary disorders3/363/37
SGOTHepatobiliary disorders3/360/37
FeverGeneral disorders2/361/37
SodiumRenal and urinary disorders2/361/37
White Blood CellsBlood and lymphatic system disorders0/362/37

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)MinocyclinePlaceboTotal
<=18 years000
Between 18 and 65 years363773
>=65 years000
Age Continuous
Age Continuous(years)MinocyclinePlaceboTotal
Mean37.3 ± 8.2136.7 ± 7.1737.0 ± 7.66
Sex: Female, Male
Sex: Female, Male(Participants)MinocyclinePlaceboTotal
Female343266
Male257
Region of Enrollment
Region of Enrollment(participants)MinocyclinePlaceboTotal
Uganda363773
Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale
Baseline Memorial Sloan Kettering (MSK) Acquired Immune Deficiency Syndrome (AIDS) Dementia Scale(Participants)MinocyclinePlaceboTotal
Equivocal/subclinical353772
Mild101
Baseline Cluster of Differentiation Four (CD4) Count
Baseline Cluster of Differentiation Four (CD4) Count(cells/mm^3)MinocyclinePlaceboTotal
Median319 (251 to 469)305 (252 to 500)313 (251 to 500)
Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL))
Baseline Log10(Human immunodeficiency virus (HIV) Ribonucleic Acid (RNA) Viral Load (VL))(copies/mL)MinocyclinePlaceboTotal
Log mean4.41 (4.09 to 4.94)4.59 (4.12 to 5.25)4.50 (4.10 to 5.10)
Baseline Karnofsky's Performance Score
Baseline Karnofsky's Performance Score(Participants)MinocyclinePlaceboTotal
80 (Karnofsky Score)123
90 (Karnofsky Score)353469
100 (Karnofsky Score)011

12 further baseline measures are reported on the registry.

08

Study locations

1 site
  • Infecious Diseas Institute
    Kampala, Uganda
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 25, 2011, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT00855062
Lead sponsor
Johns Hopkins University
Collaborators
Makerere University
First posted
Mar 3, 2009
Start date
Apr 2008
Primary completion
Dec 2009
Completion
Dec 2009
Results posted
Feb 25, 2011
Last update
Feb 25, 2011

Study contacts

Ned Sacktor, MD
principal investigator · Johns Hopkins School of Medicine

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is terminated, as verified in Jan 2011. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Cognitive Dysfunction→

Other studies from this sponsor

Johns Hopkins University

Start the discussion