Results from a placebo-controlled study supported by the National Institute of Mental Health (NIMH) provide no evidence that Peptide T has an effect on neuropsychological performance in HIV seropositive individuals with cognitive impairment. Initial analyses of the primary efficacy data indicate that there were no statistically significant differences between the treatment and placebo groups with respect to overall neuropsychological functioning (the primary outcome) nor in any of seven separately measured cognitive functions. Further data analyses are pending.
The study was designed as a prospective, randomized, double-blind trial to determine whether Peptide T, administered intranasally, was effective in improving cognitive functioning in people with HIV-associated cognitive impairment.
Two hundred and fifteen participants were randomly assigned to one of two treatment groups. Peptide T was given to half the participants for six months while the remaining participants received placebo. The study was double-blind, meaning that neither physicians nor study participants knew whether the participant was assigned to the Peptide T group or the placebo group.
At the end of the first six months of the study (the double-blind phase), study participants were placed on open label Peptide T for an additional six months. At the end of twelve months, participants were given the option to continue receiving open label Peptide T until efficacy analyses were completed.
Participants were permitted to continue whatever anti-viral therapy and prophylaxis for opportunistic infections that they had been taking prior to enrolling in the study. Patients were excluded from the study if they had an active AIDS-defining opportunistic infection or malignancy likely to require chemotherapy during the time of the study, were currently using psychoactive agents or abusing drugs or alcohol.
In 1991, a co-exclusive license was granted to two companies that have the responsibility to pursue this technology and perform additional studies as indicated. Inquiries regarding the future development of Peptide T should be addressed to the co-licensees: Advanced Peptides and Peptech (USA).
General information about HIV disease, testing, or treatment options may be obtained from health care providers, state and local health departments or by calling any of the following numbers:
Additional funding for the study was provided by the National Institute of Allergy and Infectious Diseases (NIAID). NIMH and NIAID are components of the National Institutes of Health, an agency of the U.S. Public Health Service, part of the U.S. Department of Health and Human Services.
Information Regarding the Phase II NIMH Clinical Trial of Peptide T
Research has shown that cognitive impairment occurs in some individuals infected with HIV.
1. What is Peptide T?
Peptide T is a synthetic compound composed of eight amino acids (octapeptide).
2. What was the therapeutic goal of Peptide T in this study?
To test the efficacy of Peptide T to treat cognitive impairment in HIV infection.
3. What was the outcome of the trial?
The study showed no evidence to suggest that Peptide T had an effect on neuropsychological performance in HIV seropositive individuals with cognitive impairment. There were no statistically significant differences between the treatment groups with respect to the global change in neuropsychological functioning (the primary outcome) nor in any of seven separately measured cognitive domains.
4. What is cognitive impairment and how is it measured?
Cognitive impairment includes difficulties with memory, attention, language, problem solving, spatial ability, and visual-motor coordination. Cognitive impairment can be measured by neuropsychological testing or by neurological/psychiatric clinical assessment.
5. What was the historical development that led to Peptide T being tested as a potential treatment for HIV-associated cognitive impairment?
Peptide T was originally developed in 1986 at the NIMH by intramural research scientists whose efforts were led by Dr. Candace Pert, formerly of NIMH.
In December 1987 the NIMH began a Phase I clinical trial of Peptide T to explore the safety and potential activity of Peptide T in treating HIV infection. In this limited trial there was some improvement in neuropsychological tests cores. A blue-ribbon panel convened by NIMH and the National Institute of Allergy and Infectious Diseases (NIAID) composed of expert researchers in the field reviewed the Phase I and supporting pre-clinical data and recommended further evaluation of Peptide T as a potential treatment for HIV-associated cognitive dysfunction in a limited Phase II controlled clinical trial. The parameters of the study (e.g., dose of Peptide T, time of treatment period, route of administration) were based on earlier Phase I experiments carried out by the developers which suggested that Peptide T affected the central nervous system. Since there were no licensees to pursue this technology in 1991, co-exclusive licenses were granted by the Department of Commerce to Advanced Peptides (formerly Integra) and Peptech (formerly Therapeutic Peptides).
6. What was the chronology of the NIMH Phase II Study of Peptide T?
In 1990, NIMH sponsored this Phase II clinical trial in collaboration with the NIAID. From mid March 1991 through the end of June 1992, the study recruited subjects at the University of Southern California in Los Angeles (USC). The number of subjects and study sites was increased in order to have adequate numbers of study participants to be able to establish efficacy and meet the needs of a pivotal Phase II clinical trial. In the fall of 1992, NIMH established two additional research sites, one at the University of Miami and the other at the University of California in San Diego (UCSD). The Principal Investigators are Dr. Peter N.R. Heseltine of the University of Southern California at Los Angeles, Dr. J. Hampton Atkinson of the University of California at San Diego, and Dr. Karl Goodkin of the University of Miami.
7. What was the design of the NIMH Phase II study?
The study was designed as a prospective, randomized, double-blind trial to determine whether the administration of intranasal Peptide T (up to 6 milligrams per day), compared to placebo, was effective in improving cognitive function in outpatients with a range of HIV-associated cognitive impairment. Participants were randomly assigned to receive either Peptide T or placebo for the first six months of the study. The study was double-blind, meaning that neither researchers nor study participants knew whether the participant was assigned to the Peptide T group or the placebo group. Following this double-blind phase, all study participants were offered the opportunity to receive Peptide T for the next six months. As is often the case in AIDS clinical trials, this study design enabled all study participants to receive Peptide T for at least six months. At the end of twelve months, participants were given the additional option to continue receiving open label Peptide T (humanitarian phase) until the results of the primary efficacy analysis were completed.
8. Who were the study participants?
Adults, ages 18-60 years, with HIV-associated cognitive impairment ranging from mild to severe.
9. How was efficacy to be determined?
The change in cognitive function was compared following six months treatment with either Peptide T or placebo. Cognitive function was ascertained with standard neuropsychological tests.
10. Were there any toxicities directly associated with Peptide T use?
To date, no overt toxicity has been noted. Complete analysis of this variable is currently underway.
An independent panel of experts, the Data Safety Monitoring Board, monitored the data of the participants throughout the course of this trial. Their task was to ensure that study participants were not being harmed because of potential toxicities. The panel found no safety concerns during the study. Deaths occurred in both arms of the study, and none were attributed to taking Peptide T.
11. Where can I obtain additional information regarding further development of Peptide T in association with HIV?
Information regarding the development of Peptide T may be ddressed to the co-licensees Advanced Peptides and Peptech USA).