Minocycline for HIV+ Cognitive Impairment in Uganda

This study has been 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.)
Sponsor:
Collaborator:
Makerere University
Information provided by:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT00855062
First received: March 2, 2009
Last updated: January 28, 2011
Last verified: January 2011

March 2, 2009
January 28, 2011
April 2008
December 2009   (final data collection date for primary outcome measure)
24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
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.
· To examine whether minocycline treatment will improve cognitive performance after 24 weeks compared to baseline [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00855062 on ClinicalTrials.gov Archive Site
  • 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
    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 Frame: Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24 ] [ Designated as safety issue: Yes ]
    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 Frame: Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At baseline and week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
    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) [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]
    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 [ Time Frame: At baseline and week 24 ] [ Designated as safety issue: No ]

    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.

  • · To examine whether minocycline treatment for 24 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • · To examine whether minocycline treatment for 48 weeks is safe and well-tolerated in individuals with HIV-associated cognitive impairment [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • · To examine whether minocycline treatment for 24 weeks improves functional impairment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Minocycline for HIV+ Cognitive Impairment in Uganda
Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda

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
Not Provided
Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • HIV-associated Cognitive Impairment
  • HIV Infections
  • Drug: minocycline
    100 mg capsule every 12 hours by mouth
  • Drug: minocycline placebo capsule
    1 capsule every 12 hours by mouth
  • Active Comparator: Minocycline
    Minocycline 100 mg orally every 12 hours
    Intervention: Drug: minocycline
  • Placebo Comparator: Placebo
    Placebo minocycline capsules every 12 hours
    Intervention: Drug: minocycline placebo capsule
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
73
December 2009
December 2009   (final data collection date for primary outcome measure)

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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
Uganda
 
NCT00855062
Uganda minocycline study, Grant Number: 5 UO1 NS32228
Yes
Ned Sacktor, MD, Johns Hopkins School of Medicine
Johns Hopkins University
Makerere University
Principal Investigator: Ned Sacktor, MD Johns Hopkins School of Medicine
Johns Hopkins University
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP