Minocycline for HIV+ Cognitive Impairment in Uganda

Phase 1

Terminated

Conditions: HIV-associated Cognitive Impairment
HIV Infections

Interventions: Drug: minocycline placebo capsule
Drug: minocycline

Registration Number: NCT00855062

Lead Sponsor: Johns Hopkins University

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

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 73

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	minocycline placebo capsule	Placebo minocycline capsules every 12 hours
Minocycline	minocycline	Minocycline 100 mg orally every 12 hours

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.