Cognition Disorders, HIV Infections
Conditions
Keywords
Acquired Immunodeficiency Syndrome, AIDS-Related Complex
Brief summary
To evaluate the chemical efficacy and safety of intranasally administered peptide T on neurocognitive function in HIV seropositive individuals. Previous studies have shown that treatment with peptide T can result in cognitive improvement in HIV-infected patients. Patients are randomized to receive either peptide T or placebo for the first 6 months. All patients then receive open-label peptide T for approximately 6 additional months. Neuropsychologic tests are used to determine drug effects.
Interventions
DRUGPeptide T
DRUGPlacebo
Sponsors
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Patients must have: 1. Cognitive dysfunction on neuropsychological testing. 2. HIV antibody positivity. 3. Expected survival of 6 months. 4. EITHER no use of an antiretroviral within the past 4 weeks OR use of approved regimens of AZT, ddI, or ddC. 5. Medically stable EKG and urinalysis. 6. Given informed, written consent to participate. * Allowed: 1. Inhaled aerosolized pentamidine for Pneumocystis carinii pneumonia prophylaxis, dapsone, cotrimoxazole, topical antifungal agents, nystatin or ketoconazole, acyclovir. 2. Amitriptyline (up to 50 mg/day) or an equivalent dose of another antidepressant for relief of peripheral neuropathy that is expected to remain unchanged throughout the first 6 months of the study. * Abstinence or agree to use barrier methods of birth control / contraception during the study * Negative pregnancy test within 30 days of study entry * Bilirubin \<= 3 * CD4 (Must be \<= 500 cells/mm3 if patient is without non-cognitive HIV-related symptoms. CD4 count \> 500 cells/mm3 allowed if patient has other (non-cognitive) HIV-related symptoms. ( 0 - 100 - 200 - 300 - 400 - 500 - 600 - 700 - 800 plus.) * Creatinine \<= 1.5 mg/dl * Granulocytes \>= 750 * Hemoglobin \> 8 g/dl (No more than two transfusions per month permitted.) * Other Lab Values Prothrombin time \> 70 percent of control. * Platelet Count \>= 75000 /mm3 * SGOT(AST) \< 5 x ULN (ULN = upper limit of normal).
Exclusion criteria
* Patients with the following are excluded: 1. History of mental retardation or learning disability. 2. Evidence of current DSM-III-R Axis I disorder within 3 months prior to study entry or past history of psychotic disorder or bipolar mania. 3. History of neurologic disorder not secondary to HIV infection (e.g., head trauma requiring medical observation or hospitalization, seizure disorder). * Patients with the following symptoms or conditions are excluded: 1. Kaposi's sarcoma or other malignancy likely to require chemotherapy during the first 6 months of the study. 2. Serious underlying medical problems that may complicate interpretation of the treatment results, including unstable diabetes mellitus, severe arteriosclerotic heart disease, uncontrolled hypertension, or hepatic or renal failure. 3. Non-HIV related condition that is likely to interfere with interpretation of neuropsychologic test results. 4. Inability to participate in neuropsychologic testing or unable to comply with intranasal study medication administration. * Excluded within 4 weeks prior to study entry: 1. Antiretrovirals except as allowed in the Patient Inclusion Criteria. 2. Psychoactive agents (e.g., benzodiazepines, antidepressants, antipsychotics, amphetamines) Excluded within 8 weeks prior to study entry: Long-acting psychoactive agents (e.g., Prozac). * Active alcohol abuse in the past 3 months, or abuse judged by the investigators as likely to interfere with the analyses of neuropsychologic function. Abuse of cocaine, marijuana, heroin or other opiates (including methadone), barbiturates, amphetamines or other substances within the past 3 months, judged by the investigators as likely to interfere with the analyses of neuropsychologic tests. * Positive pregnancy test within 30 days of study entry * No abstinence or no agreement to use barrier methods of birth control / contraception during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Global Neurocognitive Performance z Score From Baseline | Baseline and 6 months | Higher values for change in z-score represent an improvement in Neurocognitive Performance (NP) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neurocognitive Performance Domain z Scores From Baseline | Baseline and 6 months | Higher values for change in z-score represent an improvement in Neurocognitive Performance (NP) |
Countries
United States
Participant flow
Pre-assignment details
Of 457 persons screened for cognitive impairment, 205 men and 10 women were randomized (106 to peptide T and 109 to placebo).
Participants by arm
| Arm | Count |
|---|---|
| Peptide T Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months
Peptide T | 106 |
| Placebo Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months
Placebo | 109 |
| Total | 215 |
Baseline characteristics
| Characteristic | Placebo | Peptide T | Total |
|---|---|---|---|
| Age, Customized 18-39 years | 62 Participants | 60 Participants | 122 Participants |
| Race/Ethnicity, Customized Black | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic | 9 Participants | 16 Participants | 25 Participants |
| Race/Ethnicity, Customized White | 94 Participants | 83 Participants | 177 Participants |
| Region of Enrollment United States | 109 participants | 106 participants | 215 participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 104 Participants | 101 Participants | 205 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 75 / 106 | 57 / 109 |
| serious Total, serious adverse events | 8 / 106 | 3 / 109 |
Outcome results
Primary
Change in Global Neurocognitive Performance z Score From Baseline
Higher values for change in z-score represent an improvement in Neurocognitive Performance (NP)
Time frame: Baseline and 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Peptide T | Change in Global Neurocognitive Performance z Score From Baseline | 0.24 z score | Standard Error 0.05 |
| Placebo | Change in Global Neurocognitive Performance z Score From Baseline | 0.16 z score | Standard Error 0.03 |
p-value: 0.18ANOVA
Secondary
Change in Neurocognitive Performance Domain z Scores From Baseline
Higher values for change in z-score represent an improvement in Neurocognitive Performance (NP)
Time frame: Baseline and 6 months
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Verbal fluency | 0.14 z score | Standard Error 0.09 |
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Visuospatial ability | 0.17 z score | Standard Error 0.06 |
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Abstract thinking | 0.34 z score | Standard Error 0.07 |
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Speed of information processing | 0.23 z score | Standard Error 0.07 |
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Working memory | 0.23 z score | Standard Error 0.09 |
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Motor performance | 0.19 z score | Standard Error 0.06 |
| Peptide T | Change in Neurocognitive Performance Domain z Scores From Baseline | Learning and retention | 0.19 z score | Standard Error 0.07 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Speed of information processing | 0.14 z score | Standard Error 0.05 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Verbal fluency | 0.15 z score | Standard Error 0.08 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Motor performance | 0.18 z score | Standard Error 0.06 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Visuospatial ability | 0.25 z score | Standard Error 0.06 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Working memory | 0.08 z score | Standard Error 0.07 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Abstract thinking | 0.23 z score | Standard Error 0.04 |
| Placebo | Change in Neurocognitive Performance Domain z Scores From Baseline | Learning and retention | 0.11 z score | Standard Error 0.06 |