HIV-associated Cognitive ImpairmentPhase 1/2NCT00855062

Minocycline for HIV+ Cognitive Impairment in Uganda

A Phase 1/2 study testing minocycline in people with HIV-associated Cognitive Impairment and HIV Infections, run by Johns Hopkins University at 1 site in Uganda.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

Search all trials

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. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: HIV-associated Cognitive Impairment, HIV Infections
What is being tested?: minocycline
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 73 participants
Where: 1 siteUganda
Study dates: Apr 2008to Dec 2009
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 10Show fewer

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

Who cannot join

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

Show all 14Show fewer

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

Trial locations and contacts

1 site in 1 country.

Uganda1 site

Infecious Diseas Institute
Kampala

Other trials in Uganda

About this study

Official title: Minocycline in the Treatment of 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

Conditions: HIV-associated Cognitive Impairment, HIV Infections
Being tested: minocycline, minocycline placebo capsule
Keywords: Human immunodeficiency virus (HIV), HIV associated cognitive impairment, HIV dementia, Uganda, Acquired immune deficiency syndrome (AIDS), Treatment Naive
Medical subject headings: HIV Infections, Acquired Immunodeficiency Syndrome, AIDS Dementia Complex

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

minocyclineDrug
100 mg capsule every 12 hours by mouth
minocycline placebo capsuleDrug
1 capsule every 12 hours by mouth

Study groups in NCT00855062
Study group	Role	What they receive
Minocycline	Active comparator	Minocycline 100 mg orally every 12 hours Receives: Drug: minocycline
Placebo	Placebo comparator	Placebo minocycline capsules every 12 hours Receives: Drug: minocycline placebo capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: At baseline and week 24

Secondary outcomes (9)

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.
Measured: At baseline and week 24
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.
Measured: At baseline and week 24
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.
Measured: Time of initial Grade ≥ 2 toxicity and/or sign and symptom event up to week 24
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.
Measured: Time of first Grade ≥ 2 toxicity and/or sign and symptom event up to 48 weeks
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.
Measured: At baseline and week 24
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.
Measured: At baseline and week 48
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.
Measured: At baseline and week 24
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.
Measured: At baseline and week 24
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.
Measured: At baseline and week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2008Dec 2009

First posted3 Mar 2009 (estimated)
Study startApr 2008
Primary completionDec 2009
Study completionDec 2009

Why it 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.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for HIV-associated Cognitive ImpairmentStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00855062
Sponsor's protocol ID: Uganda minocycline study
Other IDs: Grant Number: 5 UO1 NS32228
Status last verified: Jan 2011
First submitted: 2 Mar 2009
Last updated: 25 Feb 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Study at a glance

From the registry record, last updated by the sponsor on 25 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Minocycline in the Treatment of HIV-Associated Cognitive Impairment in Uganda
ClinicalTrials.gov ID: NCT00855062
Acronym / sponsor ID: Uganda minocycline study
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
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason 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.
Enrolment: 73 participants (actual)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Collaborators: Makerere University
Study start: Apr 2008
Primary completion: Dec 2009 (actual)
Study completion: Dec 2009 (actual)
First posted: 3 Mar 2009 (estimated)
Results: Posted 25 Feb 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Single group
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Minocycline	Active comparator	Drug: minocyclineMinocycline 100 mg orally every 12 hours
Placebo	Placebo comparator	Drug: minocycline placebo capsulePlacebo minocycline capsules every 12 hours

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

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

Key exclusion criteria (14 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
minocycline100 mg capsule every 12 hours by mouth	Drug	Minocycline
minocycline placebo capsule1 capsule every 12 hours by mouth	Drug	Placebo

Primary outcome

24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)
Time frame: 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.

9 secondary outcomes

24-week Change of Memorial Sloan Kettering (MSK) HIV Dementia Stage
Time frame: At baseline and week 24
24-week Change of Karnofsky Performance Score
Time frame: At baseline and week 24
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
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
24-week Change of CD4 Cell Counts
Time frame: At baseline and week 24
48-week Change of CD4 Cell Counts
Time frame: At baseline and week 48
24-week Change of Instrumental Activities of Daily Living
Time frame: At baseline and week 24
24-week Change of HIV RNA Plasma Viral Loads (Log10 Transformed)
Time frame: At baseline and week 24
24-week Change of Center for Epidemiologic Studies Depression (CES-D) Score
Time frame: At baseline and week 24

Results and safety

Results posted to the registry on 25 Feb 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Minocycline	36	26
Placebo	37	26

Primary outcome: 24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum)

Time frame: At baseline and week 24. Mean (Standard Deviation). Unit: z-score

Measure	Minocycline n = 30	Placebo n = 29
Value	0.44 (0.74)	0.49 (0.67)

Minocycline vs Placebo: Slope: -0.026 (95% CI -0.512 to 0.460), p = 0.370, Regression, Linear

Population analysed: The descriptive statistics are based on per protocol analysis. For the statistical analysis, ITT analysis was used and the missing U NP Sums at week 24 were imputed using a multiple regression imputation method. The number of participants analyzed for the ITT analysis was 73 (36 for Minocycline and 37 for Placebo).

9 secondary outcomes are reported in the full results.

Adverse events

Time frame: 48 weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Minocycline	2 of 36 (5.6%)	26 of 36 (72.2%)	Not reported
Placebo	1 of 37 (2.7%)	25 of 37 (67.6%)	Not reported

Limitations and caveats (from the sponsor): The estimated sample size was 100; however, due to early termination of the study, the total number of randomized participants was 73.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ned Sacktor, MD principal investigator

Johns Hopkins School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing minocycline in people with HIV-associated Cognitive Impairment and HIV Infections, run by Johns Hopkins University at 1 site in Uganda.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 25 Feb 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Uganda. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

24-week Change of Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) (time frame: At baseline and week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00855062.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2011.