Phase II Study of the Efficacy of Peptide T in HIV-Positive Individuals With Cognitive Impairment.

• Sponsor: National Institute of Mental Health (NIMH) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00000392
• Collaborator: (none)
• Enrollment: 215
• Locations: 3
• Arms: 2
• Duration (Months): 79
• Patients Per Site: 71.7
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Cognition Disorders	Drug: Peptide T; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 215 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Phase II Study of the Efficacy of Peptide T in HIV-Positive Individuals With Cognitive Impairment.
• Study Start Date: Jan 1, 1990
• Actual Primary Completion Date: Aug 1, 1996
• Actual Study Completion Date: Aug 1, 1996

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Peptide T Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months	Drug: Peptide T
Placebo Comparator: Placebo Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months	Drug: Placebo

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
2	UCSD	San Diego	California	United States	92103
3	Univ of Miami School of Medicine	Miami	Florida	United States	33136

Sponsors and Collaborators

• National Institute of Mental Health (NIMH)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

• Heseltine PN, Goodkin K, Atkinson JH, Vitiello B, Rochon J, Heaton RK, Eaton EM, Wilkie FL, Sobel E, Brown SJ, Feaster D, Schneider L, Goldschmidts WL, Stover ES. Randomized double-blind placebo-controlled trial of peptide T for HIV-associated cognitive impairment. Arch Neurol. 1998 Jan;55(1):41-51.

• Responsible Party: National Institute of Mental Health (NIMH)
• ClinicalTrials.gov Identifier: NCT00000392
• Other Study ID Numbers: N01 MH00013
• First Posted: Jan 18, 2000
• Last Update Posted: Feb 28, 2017
• Last Verified: Oct 1, 2013

• Keywords provided by National Institute of Mental Health (NIMH): Acquired Immunodeficiency Syndrome; AIDS-Related Complex
• Additional relevant MeSH terms: Cognitive Dysfunction; Cognition Disorders

Study Results

Participant Flow

Pre-assignment Detail	Of 457 persons screened for cognitive impairment, 205 men and 10 women were randomized (106 to peptide T and 109 to placebo).

Arm/Group Title	Peptide T	Placebo
Arm/Group Description	Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months Peptide T	Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months Placebo
Period Title: Overall Study
STARTED	106	109
COMPLETED	66	77
NOT COMPLETED	40	32

Baseline Characteristics

Arm/Group Title	Peptide T	Placebo	Total
Arm/Group Description	Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months Peptide T	Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months Placebo	Total of all reporting groups
Overall Participants	106	109	215
Age, Customized (Number) [Number]
18-39 years	60 56.6%	62 56.9%	122 56.7%
Sex: Female, Male (Count of Participants)
Female	5 4.7%	5 4.6%	10 4.7%
Male	101 95.3%	104 95.4%	205 95.3%
Race/Ethnicity, Customized (Number) [Number]
White	83 78.3%	94 86.2%	177 82.3%
Hispanic	16 15.1%	9 8.3%	25 11.6%
Black	5 4.7%	5 4.6%	10 4.7%
Region of Enrollment (participants) [Number]
United States	106 100%	109 100%	215 100%

Outcome Measures

1. Primary Outcome

Title	Change in Global Neurocognitive Performance z Score From Baseline
Description	Higher values for change in z-score represent an improvement in Neurocognitive Performance (NP)
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peptide T	Placebo
Arm/Group Description	Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months Peptide T	Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months Placebo
Measure Participants	66	77
Mean (Standard Error) [z score]	0.24 (0.05)	0.16 (0.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Peptide T, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.18
	Comments
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Change in Neurocognitive Performance Domain z Scores From Baseline
Description	Higher values for change in z-score represent an improvement in Neurocognitive Performance (NP)
Time Frame	Baseline and 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Peptide T	Placebo
Arm/Group Description	Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months Peptide T	Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months Placebo
Measure Participants	66	77
Verbal fluency	0.14 (0.09)	0.15 (0.08)
Visuospatial ability	0.17 (0.06)	0.25 (0.06)
Abstract thinking	0.34 (0.07)	0.23 (0.04)
Speed of information processing	0.23 (0.07)	0.14 (0.05)
Working memory	0.23 (0.09)	0.08 (0.07)
Learning and retention	0.19 (0.07)	0.11 (0.06)
Motor performance	0.19 (0.06)	0.18 (0.06)

Adverse Events

Adverse Event Reporting Description	Only data for the events that were statistically significant between the two treatment groups could be retrieved because adverse event data are lost.
Arm/Group Title	Peptide T		Placebo
Arm/Group Description	Peptide T given intranasally at a dosage of 2mg 3 times a day for 6 months Peptide T		Placebo given intranasally at a dosage of 2mg 3 times a day for 6 months Placebo
All Cause Mortality
	Peptide T		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Peptide T		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/106 (7.5%)		3/109 (2.8%)
Immune system disorders
Death	8/106 (7.5%)		3/109 (2.8%)
Other (Not Including Serious) Adverse Events
	Peptide T		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/106 (70.8%)		57/109 (52.3%)
Blood and lymphatic system disorders
Eosinophilia	4/106 (3.8%)		0/109 (0%)
Psychiatric disorders
Depression or Irritability	7/106 (6.6%)		1/109 (0.9%)
Renal and urinary disorders
Proteinuria	18/106 (17%)		9/109 (8.3%)
Respiratory, thoracic and mediastinal disorders
Nasal Congestion	12/106 (11.3%)		5/109 (4.6%)
Skin and subcutaneous tissue disorders
Rash	34/106 (32.1%)		42/109 (38.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.