AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial

Soraya Allas, Assumpta Caixàs, Christine Poitou, Muriel Coupaye, Denise Thuilleaux, Françoise Lorenzini, Gwenaëlle Diene, Antonino Crinò, Frédéric Illouz, Graziano Grugni, Diane Potvin, Sarah Bocchini, Thomas Delale, Thierry Abribat, Maithé Tauber

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Context and objective Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.

Original languageEnglish
Article numbere0190849
JournalPLoS One
Volume13
Issue number1
DOIs
Publication statusPublished - Jan 1 2018

Fingerprint

Prader-Willi Syndrome
Hyperphagia
ghrelin
overeating
Ghrelin
placebos
Randomized Controlled Trials
Placebos
Food
Glucose
Appetite
appetite
body weight
questionnaires
Body Weight
Animals
Safety
Fats
Hormones
glycemic control

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome : A randomized placebo-controlled trial. / Allas, Soraya; Caixàs, Assumpta; Poitou, Christine; Coupaye, Muriel; Thuilleaux, Denise; Lorenzini, Françoise; Diene, Gwenaëlle; Crinò, Antonino; Illouz, Frédéric; Grugni, Graziano; Potvin, Diane; Bocchini, Sarah; Delale, Thomas; Abribat, Thierry; Tauber, Maithé.

In: PLoS One, Vol. 13, No. 1, e0190849, 01.01.2018.

Research output: Contribution to journalArticle

Allas, S, Caixàs, A, Poitou, C, Coupaye, M, Thuilleaux, D, Lorenzini, F, Diene, G, Crinò, A, Illouz, F, Grugni, G, Potvin, D, Bocchini, S, Delale, T, Abribat, T & Tauber, M 2018, 'AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial', PLoS One, vol. 13, no. 1, e0190849. https://doi.org/10.1371/journal.pone.0190849
Allas, Soraya ; Caixàs, Assumpta ; Poitou, Christine ; Coupaye, Muriel ; Thuilleaux, Denise ; Lorenzini, Françoise ; Diene, Gwenaëlle ; Crinò, Antonino ; Illouz, Frédéric ; Grugni, Graziano ; Potvin, Diane ; Bocchini, Sarah ; Delale, Thomas ; Abribat, Thierry ; Tauber, Maithé. / AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome : A randomized placebo-controlled trial. In: PLoS One. 2018 ; Vol. 13, No. 1.
@article{b2c0ce4ae6de40c68d63a6a78b406c4f,
title = "AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome: A randomized placebo-controlled trial",
abstract = "Context and objective Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.",
author = "Soraya Allas and Assumpta Caix{\`a}s and Christine Poitou and Muriel Coupaye and Denise Thuilleaux and Fran{\cc}oise Lorenzini and Gwena{\"e}lle Diene and Antonino Crin{\`o} and Fr{\'e}d{\'e}ric Illouz and Graziano Grugni and Diane Potvin and Sarah Bocchini and Thomas Delale and Thierry Abribat and Maith{\'e} Tauber",
year = "2018",
month = "1",
day = "1",
doi = "10.1371/journal.pone.0190849",
language = "English",
volume = "13",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "1",

}

TY - JOUR

T1 - AZP-531, an unacylated ghrelin analog, improves food-related behavior in patients with Prader-Willi syndrome

T2 - A randomized placebo-controlled trial

AU - Allas, Soraya

AU - Caixàs, Assumpta

AU - Poitou, Christine

AU - Coupaye, Muriel

AU - Thuilleaux, Denise

AU - Lorenzini, Françoise

AU - Diene, Gwenaëlle

AU - Crinò, Antonino

AU - Illouz, Frédéric

AU - Grugni, Graziano

AU - Potvin, Diane

AU - Bocchini, Sarah

AU - Delale, Thomas

AU - Abribat, Thierry

AU - Tauber, Maithé

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Context and objective Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.

AB - Context and objective Prader-Willi syndrome (PWS) is characterized by early-onset hyperphagia and increased circulating levels of the orexigenic Acylated Ghrelin (AG) hormone with a relative deficit of Unacylated Ghrelin (UAG). AZP-531, a first-in-class UAG analog, was shown to inhibit the orexigenic effect of AG in animals, to improve glycemic control and decrease body weight in humans. We aimed to investigate the safety and efficacy of AZP-531 in patients with PWS for whom no approved treatment for hyperphagia is currently available. Methods and design Multi-center, randomized, double-blind, placebo-controlled trial. Forty-seven patients with genetically confirmed PWS and evidence of hyperphagia received daily subcutaneous injections of AZP-531 (3 and 4 mg for 50–70 kg and >70 kg body weight, respectively) or matching placebo for 14 days. Assessments included adverse events, vital signs, safety laboratory tests, the Hyperphagia Questionnaire (HQ), patient-reported appetite, body composition and glycemic measures. Results AZP-531 was well tolerated. There was a significant improvement with AZP-531 versus placebo in the mean total score, the 9-item score and the severity domain score of the HQ (p < .05). The highest reduction in the total and 9-item scores was observed in AZP-531 subjects with the highest hyperphagia score at baseline. Findings were supported by a reduction in appetite scores observed with AZP-531 only. Body weight did not change in both groups while a significant reduction in waist circumference and fat mass was observed only with AZP-531. AZP-531 significantly decreased post-prandial glucose levels in a baseline glucose dependent fashion. Conclusions AZP-531 may constitute a new treatment strategy to improve hyperphagia and metabolic issues in patients with PWS. These findings support further investigation in longer-term clinical trials.

UR - http://www.scopus.com/inward/record.url?scp=85040362712&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85040362712&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0190849

DO - 10.1371/journal.pone.0190849

M3 - Article

C2 - 29320575

AN - SCOPUS:85040362712

VL - 13

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 1

M1 - e0190849

ER -