Effects of Tesamorelin on Neurocognitive Impairment in Persons With HIV and Abdominal Obesity.
This 6-month phase 2 randomized open-label clinical trial investigated whether tesamorelin, a growth hormone-releasing hormone analog, could improve neurocognitive impairment (NCI) in people with HIV who were virally suppressed on antiretroviral therapy and had abdominal obesity (elevated waist circumference). Seventy-three participants were randomized 3:2 to tesamorelin or standard of care (SOC). The primary outcome was change in neurocognitive performance at 6 months; secondary outcomes included waist circumference, mood, and daily functioning. The tesamorelin group showed a non-significant trend toward improved neurocognitive performance (mean change 0.146; P=.060), while the SOC group did not improve (P=.295); crucially, the between-group difference was not statistically significant (P=.673). Tesamorelin did produce a significantly greater reduction in waist circumference versus SOC (median difference −2.7 cm; P=.015). IGF-1 levels rose in the tesamorelin group but did not correlate with cognitive or waist circumference changes. Key limitations include an open-label (non-placebo-controlled) design, modest sample size resulting in insufficient statistical power, and the relatively short 6-month follow-up. The authors concluded there was no clear cognitive benefit from short-term abdominal obesity reduction with tesamorelin in this population.
Why this grade: Although conducted in humans with randomization, the trial was open-label (no placebo arm), underpowered (n=73), and found no significant between-group difference in its primary endpoint, substantially limiting the strength of conclusions.
Background In people with HIV who are virally suppressed with antiretroviral therapy, abdominal obesity (AO) is linked to neurocognitive impairment (NCI), potentially due to visceral adiposity, inflammation, and reduced insulin-like growth factor 1 (IGF-1). Tesamorelin, a growth hormone-releasing hormone, reduces AO and increases IGF-1, suggesting that it might mitigate NCI in people with HIV and viral suppression. Methods This 6-month phase 2 randomized open-label clinical trial compared tesamorelin vs standard of care (SOC) for NCI in people with HIV who were virally suppressed and abdominally obese (elevated waist circumference [WC]). Exclusions included conditions other than HIV causing NCI, active substance use disorder, and malignancy. Results Seventy-three participants were randomized 3:2 to tesamorelin or SOC (2 mg subcutaneously daily). The primary outcome was the change in neurocognitive performance at 6 months, with secondary outcomes including WC, mood, and daily functioning. The groups were well matched at baseline. The tesamorelin group showed a trend toward improved neurocognitive performance after 6 months (mean change, 0.146; 95% CI, -.002 to .294; P = .060) while the SOC group did not (0.103; 95% CI, -.095 to .301; P = .295), but the between-group difference was not significant (P = .673). IGF-1 levels increased, but changes did not correlate with summary regression change score or WC. The tesamorelin group had a greater reduction in WC than the SOC group (median difference, -2.7 cm; P = .015). Conclusions While tesamorelin reduced WC, the cognitive benefits did not significantly differ between groups. Recognizing the limitations of insufficient power and no placebo arm, this study suggests no clear benefit of short-term AO reduction with tesamorelin on NCI.
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