Evaluating the Safety and Efficacy of Capromorelin in Rhesus Macaques (Macaca mulatta)

Abstract

Nonhuman primates used in biomedical research may experience clinically significant weight loss for a variety of reasons. Episodes of anorexia (complete loss of appetite) or hyporexia (decreased appetite) can result in significant weight loss, potentially altering animal welfare and scientific studies. The FDA has approved several appetite stimulants for use in domestic species, but currently none are approved for use in NHP. Treatment of inappetence and weight loss in NHP often relies on the extralabel use of these compounds. Capromorelin is a ghrelin receptor agonist. As a growth hormone secretagogue, capromorelin increases appetite, leading to weight gain. Studies in several species have shown a positive correlation between capromorelin administration and weight gain; in 2017, an oral solution of capromorelin received FDA approval for use in dogs. We tested this solution in healthy adult rhesus macaques (n = 3 males and 3 females) for its effects on body weight and insulin like growth factor-1 (IGF-1). A control group (n = 2 males and 2 females) was used for comparison. Treated macaques received a 3mg/kg oral dose daily for 7 d. Clinical signs were observed daily. Weights were collected before, during and at the end of treatment. Blood was drawn before, during and after treatment for measurement of IGF-1 levels and standard hematology and biochemistry parameters. Baseline-adjusted mean body weights and IGF-1 levels were significantly higher in treated as compared with control monkeys after 7 d of beginning treatment (body weight of 10.5±0.1kg (mean ± SEM) and 10.1±0.1kg, respectively; IGF-1 of 758±43ng/mL and 639±22ng/mL, respectively). Capromorelin administration was not associated with appreciable changes in hematologic and biochemical values in treated macaques. These findings suggest that capromorelin may be useful for treating inappetence and weight loss in NHP, and based on blood analysis, a 7-d course of treatment does not appear to cause acute toxicity.

Figure 1.

Study Design including manipulations done to Control (C) and Experimental animals (E) over the course of the 14 days. Manipulations performed during days 1-7 denoted within ( ). Manipulations performed during days 8-14 denoted with [ ].

Figure 2.

Mean weights for treated (solid line) and untreated (dashed line) macaques over the course of the 14-d study. The vertical bars are the 95% CIs.

Figure 3.

Adjusted weights of treated (solid line) and control (broken line) macaques over the course of the 14-d study.

Figure 4.

IGF-1 levels of experimental animals (solid line) and control animals (broken line) over the course of days 8 to 14. Time 0, 4 h post, and 8 h post all occurred on day 8.

Figure 5.

IGF-1 levels adjusted for experimental animals (solid line) and control animals (broken line) over the course of days 8 to 14. Time 0, 4 h post, and 8 h post occurred on day 8.