Clinical trial NCT00855062: Minocycline for HIV+ Cognitive Impairment in Uganda
Official title: Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: 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
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: Makerere University
First posted: 2009-03-03
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
timeFrame: At baseline and week 24
Secondary outcomes:
measure: 24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage
timeFrame: At baseline and week 24
measure: 24-week Change of Karnofsky Performance Score
timeFrame: At baseline and week 24
measure: Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms.
timeFrame: Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24
measure: Time From Treatment Initiation to the Development of a Grade ≥ 2 Toxicity and/or Sign and Symptoms
timeFrame: Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks
measure: 24-week Change of CD4 Cell Counts
timeFrame: At baseline and week 24
measure: 48-week Change of CD4 Cell Counts
timeFrame: At baseline and week 48
measure: 24-week Change of Instrumental Activities of Daily Living
timeFrame: At baseline and week 24
measure: 24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)
timeFrame: At baseline and week 24
measure: 24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score
timeFrame: At baseline and week 24
Other outcomes:
Locations:
city: Kampala
country: Uganda
facility: Infecious Diseas Institute
Study officials:
affiliation: Johns Hopkins School of Medicine
name: Ned Sacktor, MD
role: PRINCIPAL_INVESTIGATOR
References: