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Minocycline for HIV+ Cognitive Impairment in Uganda

Primary Purpose

HIV-associated Cognitive Impairment, HIV Infections

Status
Terminated
Phase
Phase 1
Locations
Uganda
Study Type
Interventional
Intervention
minocycline
minocycline placebo capsule
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV-associated Cognitive Impairment focused on measuring Human immunodeficiency virus (HIV), HIV associated cognitive impairment, HIV dementia, Uganda, Acquired immune deficiency syndrome (AIDS), Treatment Naive

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Infecious Diseas Institute

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Minocycline

Placebo

Arm Description

Minocycline 100 mg orally every 12 hours

Placebo minocycline capsules every 12 hours

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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 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 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.
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.
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.
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.
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.
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.

Full Information

First Posted
March 2, 2009
Last Updated
January 28, 2011
Sponsor
Johns Hopkins University
Collaborators
Makerere University
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1. Study Identification

Unique Protocol Identification Number
NCT00855062
Brief Title
Minocycline for HIV+ Cognitive Impairment in Uganda
Official Title
Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda
Study Type
Interventional

2. Study Status

Record Verification Date
January 2011
Overall Recruitment Status
Terminated
Why Stopped
The Neurologic AIDS Research Consortium Data Safety and Monitoring Board committee recommended to terminate the study early due to futility on 11/6/2009.
Study Start Date
April 2008 (undefined)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Johns Hopkins University
Collaborators
Makerere University

4. Oversight

Data Monitoring Committee
Yes

5. 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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Minocycline
Arm Type
Active Comparator
Arm Description
Minocycline 100 mg orally every 12 hours
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo minocycline capsules every 12 hours
Intervention Type
Drug
Intervention Name(s)
minocycline
Intervention Description
100 mg capsule every 12 hours by mouth
Intervention Type
Drug
Intervention Name(s)
minocycline placebo capsule
Intervention Description
1 capsule every 12 hours by mouth
Primary Outcome Measure Information:
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
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ned Sacktor, MD
Organizational Affiliation
Johns Hopkins School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Infecious Diseas Institute
City
Kampala
Country
Uganda

12. IPD Sharing Statement

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Minocycline for HIV+ Cognitive Impairment in Uganda

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