Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment

Peter N R Heseltine, Karl Goodkin, J. Hampton Atkinson, Benedetto Vitiello, James Rochon, Robert K. Heaton, Elaine M. Eaton, Frances L. Wilkie, Eugene Sobel, Stephen J. Brown, Daniel J Feaster, Lon Schneider, Walter L. Goldschmidts, Ellen S. Stover

Research output: Contribution to journalArticle

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Abstract

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).

Original languageEnglish
Pages (from-to)41-51
Number of pages11
JournalArchives of Neurology
Volume55
Issue number1
DOIs
StatePublished - Apr 8 1998
Externally publishedYes

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Peptide T
Placebos
HIV
CD4 Lymphocyte Count
Cognition
Therapeutics
Cognitive Dysfunction
AIDS/HIV
Placebo
Cognitive Impairment
Controlled
Intranasal Administration
Poisons
Virus Diseases
Random Allocation
Dementia
Acquired Immunodeficiency Syndrome
Outcome Assessment (Health Care)
Cells
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Heseltine, P. N. R., Goodkin, K., Atkinson, J. H., Vitiello, B., Rochon, J., Heaton, R. K., ... Stover, E. S. (1998). Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment. Archives of Neurology, 55(1), 41-51. https://doi.org/10.1001/archneur.55.1.41

Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment. / Heseltine, Peter N R; Goodkin, Karl; Atkinson, J. Hampton; Vitiello, Benedetto; Rochon, James; Heaton, Robert K.; Eaton, Elaine M.; Wilkie, Frances L.; Sobel, Eugene; Brown, Stephen J.; Feaster, Daniel J; Schneider, Lon; Goldschmidts, Walter L.; Stover, Ellen S.

In: Archives of Neurology, Vol. 55, No. 1, 08.04.1998, p. 41-51.

Research output: Contribution to journalArticle

Heseltine, PNR, Goodkin, K, Atkinson, JH, Vitiello, B, Rochon, J, Heaton, RK, Eaton, EM, Wilkie, FL, Sobel, E, Brown, SJ, Feaster, DJ, Schneider, L, Goldschmidts, WL & Stover, ES 1998, 'Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment', Archives of Neurology, vol. 55, no. 1, pp. 41-51. https://doi.org/10.1001/archneur.55.1.41
Heseltine, Peter N R ; Goodkin, Karl ; Atkinson, J. Hampton ; Vitiello, Benedetto ; Rochon, James ; Heaton, Robert K. ; Eaton, Elaine M. ; Wilkie, Frances L. ; Sobel, Eugene ; Brown, Stephen J. ; Feaster, Daniel J ; Schneider, Lon ; Goldschmidts, Walter L. ; Stover, Ellen S. / Randomized double-blind placebo-controlled trial of peptide T for HIV- associated cognitive impairment. In: Archives of Neurology. 1998 ; Vol. 55, No. 1. pp. 41-51.
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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, Daniel J

AU - Schneider, Lon

AU - Goldschmidts, Walter L.

AU - Stover, Ellen S.

PY - 1998/4/8

Y1 - 1998/4/8

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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