Minocycline for HIV+ Cognitive Impairment in Uganda

HIV Infections Clinical Trial

Official title:

Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00855062
• Other study ID #: Uganda minocycline study
• Secondary ID: Grant Number: 5
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: March 2, 2009
• Last updated: January 28, 2011
• Start date: April 2008
• Est. completion date: December 2009

Study information

• Verified date: January 2011
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: NINDS appointed Data Safety Monitoring Committee for the Neurologic AIDS Research Consortium
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 73
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cognition Disorders
• HIV Infections
• HIV-associated Cognitive Impairment

Intervention

Drug:
• minocycline
100 mg capsule every 12 hours by mouth
• minocycline placebo capsule
1 capsule every 12 hours by mouth

Locations

Country	Name	City	State
Uganda	Infecious Diseas Institute	Kampala

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	Makerere University

Country where clinical trial is conducted

Uganda, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At baseline and week 24	No
Secondary	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.	At baseline and week 24	No
Secondary	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.	At baseline and week 24	No
Secondary	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 of initial Grade = 2 toxicity and/or sign and symptom event up to week 24	Yes
Secondary	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 of first Grade = 2 toxicity and/or sign and symptom event up to 48 weeks	Yes
Secondary	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.	At baseline and week 24	No
Secondary	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.	At baseline and week 48	No
Secondary	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.	At baseline and week 24	No
Secondary	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.	At baseline and week 24	No
Secondary	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.	At baseline and week 24	No