TY - JOUR
T1 - Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment
AU - Heseltine, Peter N.R.
AU - Goodkin, Karl
AU - Atkinson, J. Hampton
AU - Vitiello, Benedetto
AU - Rochon, James
AU - Heaton, Robert K.
AU - Eaton, Elaine M.
AU - Wilkie, Frances L.
AU - Sobel, Eugene
AU - Brown, Stephen J.
AU - Feaster, Dan
AU - Schneider, Lon
AU - Goldschmidts, Walter L.
AU - Stover, Ellen S.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - Background: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala- peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. Objective: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. Patients and Methods: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. Results: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P=.07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4+ cell count was above 0.200x 109/L (200 cells/μL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P=.02; Mantel-Haenszel X2 test). Conclusions: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score ≤0.5) or with relatively preserved immunological status (ie, CD4+ cell count >0.200X 109/L).
AB - Background: Cognitive impairment is a common consequence of human immunodeficiency virus (HIV) infection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala- peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of peptide T to HIV-positive patients with cognitive impairment was associated with improvement in cognition and constitutional symptoms. Objective: To determine whether the intranasal administration of peptide T would improve cognitive function of HIV-positive patients with cognitive impairment. Patients and Methods: This was a 3-site, double-blind, placebo-controlled trial of peptide T given intranasally at a dosage of 2 mg 3 times a day for 6 months. Participants were HIV-seropositive persons with evidence of cognitive deficits on a screening test battery. Concomitant antiretroviral therapy was allowed. Randomization to the 2 study arms was balanced according to several stratification variables, such as CD4+ cell count, severity of cognitive impairment, and antiretroviral therapy at study entry. A comprehensive neuropsychological (NP) battery, which yielded 23 scores, was administered at baseline and the study end point. The primary outcome measure was a global NP score derived from the 23 standardized scores. The efficacy end point was the change in NP score at 6 months compared with baseline. Secondary efficacy measures were 7 cognitive domain scores and deficit scores of global and domain performance. The patients who completed the baseline and final NP evaluations (after at least 4 months in the randomized treatment arm) were included in the efficacy analyses. Additional analyses were conducted on subgroups of patients according to the CD4+ count and baseline NP deficit. The incidence of NP improvement in the 2 treatment arms was also compared. Results: There was no statistically significant difference between the peptide T and placebo groups on the global NP change score, the individual domains, or the deficit scores. Because of an imbalance in the baseline CD4+ cell count between treatment arms, analyses were also adjusted for this variable. These CD4+-adjusted analyses suggested (P=.07; analysis of covariance [ANCOVA]) a greater improvement in the peptide T group. Subgroup analyses indicated a treatment effect for patients whose CD4+ cell count was above 0.200x 109/L (200 cells/μL) at baseline. Moreover, peptide T treatment was associated with overall cognitive improvement in patients with baseline global deficit scores of at least 0.5, while overall deterioration was more common among the placebo group (P=.02; Mantel-Haenszel X2 test). Conclusions: Peptide T was not significantly different from placebo on the study primary end points. However, additional analyses indicated that peptide T may be associated with improved performance in the subgroup of patients with more evident cognitive impairment (ie, NP global deficit score ≤0.5) or with relatively preserved immunological status (ie, CD4+ cell count >0.200X 109/L).
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U2 - 10.1001/archneur.55.1.41
DO - 10.1001/archneur.55.1.41
M3 - Article
C2 - 9443710
AN - SCOPUS:14444287278
SN - 0003-9942
VL - 55
SP - 41
EP - 51
JO - Archives of neurology
JF - Archives of neurology
IS - 1
ER -