Effects of an Oral Growth Hormone Secretagogue in Older Adults

White, Heidi K.; Petrie, Charles D.; Landschulz, William; MacLean, David B.; Taylor, Ann M.; Lyles, Kenneth W.; Wei, Jeanne Y.; Hoffman, Andrew R.; Salvatori, Roberto; Ettinger, Mark P.; Morey, Miriam C.; Blackman, Marc R.; Merriam, George R.

doi:10.1210/jc.2008-0632

Cited by 142 publications

(103 citation statements)

References 37 publications

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“…Even with slightly more variance in the pharmacokinetic parameters for the SCI group it was evident that the pharmacokinetic behaviour in both groups was broadly similar, with both groups displaying dose-dependent increases in drug exposure (AUC 0-∞ ) and concentration (C max; Figures 4a and b). The similarity between groups in pharmacokinetic behaviour with ascending oral doses up to 100 mg and a lack of intolerance demonstrated in this study along with the previous safe administration of 10 mg oral doses twice daily for a 12-month period 9 help to assure the safe performance in future studies that may trial this compound in SCI patients.…”

Section: Discussionmentioning

confidence: 60%

“…5 These results are consistent with the safety profile of oral capromorelin reported in previous human studies using either single 20 mg dose 11 or multi-dose (10 mg twice daily for 12 months) regimens. 9 Of interest was the absence of any effect on participants' blood pressure as had been reported in preclinical animal studies. 6 This may reflect differences in blood pressure control between species, lower relative doses used in the human study or differences in route of administration Figure 1 Blood pressure data in SCI participants at each dose level for the period from pre-dose to +12 h post dose (open squares systolic, filled squares diastolic, Mean ± s.e.m., n = 4-6).…”

Section: Discussionmentioning

confidence: 99%

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Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers

et al. 2014

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Study design: Single centre, single ascending dose study. Objectives: To compare the pharmacokinetics and assess the safety of capromorelin, a compound that has potential to treat constipation following spinal cord injury (SCI), in groups of able-bodied and SCI volunteers. Setting: Local population from Victoria, Australia. Methods: Following initial screening and baseline blood collections, participants received ascending oral doses (20, 50 and then 100 mg at least 1-week apart) of capromorelin after pre-dose blood collection, followed by blood collections over the following 12 h for pharmacokinetic analysis and 1-week and 4-week follow-up blood collections for safety evaluations. Blood pressure and heart rate were monitored. Results: No serious adverse events were recorded following any dose in either the able-bodied group or the SCI group. There were no abnormal blood pressure or heart rate changes. Minor adverse events resolved quickly without the need for treatment. Pharmacokinetic behaviour was broadly similar between groups, with both exhibiting dose-dependent increases in C max and AUC 0-∞ . The SCI participants showed greater variance in pharmacokinetic parameters and had a slightly delayed T max and half-life. Conclusion: Capromorelin at the doses tested was safe and well tolerated in both SCI and able-bodied participants and also showed similar pharmacokinetics with dose-dependent increases in concentration and drug exposure.

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers

et al. 2014

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“…Low serum levels of IGF1 and IGFBP3 were reported to be associated with poorer muscular strength, walking speed, mobility tasks, various physical performance, and all-cause mortality in the elderly (9)(10)(11)(12). GH therapy has been associated with increased lean body mass and decreased fat mass (13)(14)(15), but evidence is still lacking on its effectiveness in improving muscle function and overall physical performance in the old. However, aforementioned studies were not consistent in their findings and did not include the group of the oldest-old subjects.…”

Section: Introductionmentioning

confidence: 99%

Circulating levels of IGF1 are associated with muscle strength in middle-aged- and oldest-old women

Taekema¹,

Ling²,

Blauw³

et al. 2011

European Journal of Endocrinology

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Objective: In aging populations, poor handgrip strength has been associated with physical disability and mortality. IGF1 is an important mediator of muscle growth and regeneration affecting muscle function. We studied the relationship between circulating levels of IGF1, its binding protein 3 (IGFBP3), and handgrip strength and physical performance in middle-aged-and oldest-old subjects. Design: Cross-sectional analysis in two different cohorts composed of middle-aged-(nZ672, mean 63.9G6.7 years) and oldest-old subjects (nZ272, all 89 years). Methods: Handgrip strength, functional performance and ability, and serum levels of IGF1 and IGFBP3 were measured in all subjects and analyzed by linear regression for men and women separately. Results: IGF1 and IGFBP3 levels declined with chronological age and were positively associated with handgrip strength in middle-aged-and oldest-old women (both, P!0.05), but not in men of either age group. Furthermore, higher serum levels of IGF1 were associated with slower walking speed in oldestold men (PZ0.012), and serum levels of IGFBP3 were positively associated with activities of daily living in the oldest-old women (PZ0.002). Conclusion: The significant relationship between IGF1 levels and muscle strength found in women but not in men suggests a gender-specific influence of IGF1 on muscle strength. Further studies are necessary to test the relationship with physical performance.

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“…We have used capromorelin because it is orally active, penetrates into the central nervous system, potent at ghrelin receptors and active and safe in human. 7 …”

Section: Introductionmentioning

confidence: 99%

Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

et al. 2011

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Methods: Rats were subjected to spinal cord contusion injury or were sham-operated. At 6 weeks after surgery, effects of capromorelin on blood pressure, heart rate and propulsive contractions of the colorectum were investigated. Results: Capromorelin caused robust propulsive activity in the colorectum soon after its application. The compound was similarly effective in naïve, sham-operated and spinal cord-injured rats. Blood pressure increases caused by capromorelin were not exaggerated after SCI, and there was no evidence of phasic blood pressure increases when the colon was contracted by the compound. Conclusion: Capromorelin is a therapeutic compound that could potentially be used to relieve constipation by triggering defecation in spinal cord-injured patients.

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Effects of an Oral Growth Hormone Secretagogue in Older Adults

Abstract: In healthy older adults at risk for functional decline, administration of the oral GHS capromorelin may improve body composition and physical function.

Cited by 142 publications

References 37 publications

Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers

Pharmacokinetics of the ghrelin agonist capromorelin in a single ascending dose Phase-I safety trial in spinal cord-injured and able-bodied volunteers

Circulating levels of IGF1 are associated with muscle strength in middle-aged- and oldest-old women

Stimulation of defecation in spinal cord-injured rats by a centrally acting ghrelin receptor agonist

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