Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa

Fazeli, Pouneh K.; Lawson, Elizabeth A.; Faje, Alexander T.; Eddy, Kamryn T.; Lee, Hang; Fiedorek, Fred T.; Breggia, Anne; Gaal, Ildiko M.; DeSanti, Rebecca; Klibanski, Anne

doi:10.4088/jcp.17m11585

Cited by 54 publications

(46 citation statements)

References 34 publications

(34 reference statements)

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“…In AN not only central [ 77 ] and peripheral [ 78 ] ghrelin expression is increased, but also ghrelin signaling and modulation are impaired as indicated by a delayed or absent postprandial decrease of ghrelin [ 64 , 91 ], the inability to suppress GH secretion adequately after glucose digestion [ 101 ] or the insufficiency of glucose elevation after exogenous ghrelin application [ 119 ], suggesting ghrelin resistance in AN ( Figure 1 ). Noteworthy, exogenous ghrelin (by raising ghrelin to supraphysiological levels) or ghrelin receptor agonists still might be able to improve the course of AN by stimulating appetite and reducing gastric discomfort leading to an increase of energy intake and body weight [ 100 , 123 , 127 ]. Since these data are derived from small pilot studies, these effects should be corroborated—or refuted—in larger clinical trials.…”

Section: Discussionmentioning

confidence: 99%

“…These findings should be followed up in patients with AN as well. Very recently, a study investigated the effects of relamorelin (subcutaneously daily over a period of four weeks), a ghrelin agonist, in an outpatient cohort ( n = 10–12/group) of AN showing a significant acceleration of gastric emptying as well as a trend towards an increase of body weight (+0.9 kg vs. 0.3 kg in the control group, p < 0.07) [ 127 ]. Again, larger follow up studies are needed.…”

Section: Effects Of Exogenous Ghrelin In Anorexia Nervosamentioning

confidence: 99%

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The Role of Ghrelin in Anorexia Nervosa

Schalla

Stengel

2018

IJMS

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Ghrelin, a 28-amino acid peptide hormone expressed in X/A-like endocrine cells of the stomach, is the only known peripherally produced and centrally acting peptide that stimulates food intake and therefore attracted a lot of attention with one major focus on the treatment of conditions where an increased energy intake or body weight gain is desired. Anorexia nervosa is an eating disorder characterized by a pronounced reduction of body weight, a disturbed body image and hormonal alterations. Ghrelin signaling has been thoroughly investigated under conditions of anorexia nervosa. The present review will highlight these alterations of ghrelin in anorexia and discuss possible treatment strategies targeting ghrelin signaling. Lastly, gaps in knowledge will be mentioned to foster future research.

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Section: Discussionmentioning

confidence: 99%

Section: Effects Of Exogenous Ghrelin In Anorexia Nervosamentioning

confidence: 99%

The Role of Ghrelin in Anorexia Nervosa

Schalla

Stengel

2018

IJMS

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“…An RCT with the ghrelin receptor agonist, ulimorelin, demonstrated symptomatic improvements over placebo in 23 hospitalized patients with diabetic gastroparesis (159). The ghrelin agonist, relamorelin, was recently tested in an RCT of 22 chronic, stable patients with AN (BMI 17.7 ± 0:4) (160), where 3 out of 10 patients dropped out due to an increased hunger sensation. Gastric emptying was shortened by the ghrelin agonist; however, there was no significant weight gain during 4 weeks of treatment (160).…”

Section: Ghrelinmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Anorexia nervosa and endocrinology: a clinical update

Støving

2019

European Journal of Endocrinology

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Anorexia nervosa is a syndrome, that is collections of symptoms, which is not defined by its etiology. The severe cases are intractable. The syndrome is associated with multiple, profound endocrine alterations which may be adaptive, reactive or etiologic. Adaptive changes potentially may be inappropriate in clinical settings such as inpatient intensive re-nutrition or in a setting with somatic comorbidity. Electrolyte levels must be closely monitored during the refeeding process, and the need for weight gain must be balanced against potentially fatal refeeding complications. An important focus of clinical research should be to identify biomarkers associated with different stages of weight loss and re-nutrition combined with psychometric data. Besides well-established peripheral endocrine actions, several hormones also are released directly to different brain areas, where they may exert behavioral and psychogenic actions that could offer therapeutic targets. We need reliable biomarkers for predicting outcome and to ensure safe re-nutrition, however, first of all we need them to explore the metabolism in anorexia nervosa to open new avenues with therapeutic targets. A breakthrough in our understanding and treatment of this whimsical disease remains. Considering this, the aim of the present review is to provide an updated overview of the many endocrine changes in a clinical perspective.

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“…We measured MAT in women randomized to either four weeks of a GHS1a receptor agonist (relamorelin) (n=7) or placebo (n=11) and found that although L4 MAT was similar in both groups before treatment (p=0.28), there was a trend towards decreased L4 MAT in the women randomized to the GHS1a receptor agonist as compared to placebo (Figure 1). The women randomized to relamorelin, the GHS1a receptor agonist, had significantly lower levels of acyl ghrelin after four weeks of treatment as compared to the placebo group [44]. Whether this decrease in MAT was due to decreased levels of endogenous acyl ghrelin (which may mediate MAT promoting effects through a receptor other than the GHS1a receptor) or due to other changes mediated by the GHS1a receptor agonist is unknown but warrants further study.…”

Section: Introductionmentioning

confidence: 99%

The paradox of marrow adipose tissue in anorexia nervosa

Fazeli

Klibanski

2019

Bone

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Anorexia nervosa (AN) is a psychiatric disorder characterized by inappropriate nutrient intake resulting in low body weight. Multiple hormonal adaptations facilitate decreased energy expenditure in this state of caloric deprivation including non-thyroidal illness syndrome, growth hormone resistance, and hypogonadotropic hypogonadism. Although these hormonal adaptations confer a survival advantage during periods of negative energy balance, they contribute to the long-term medical complications associated with AN, the most common of which is significant bone loss and an increased risk of fracture. In recent years, marrow adipose tissue (MAT) has emerged as an important potential determinant of the low bone mass state characteristic of AN. Unlike subcutaneous and visceral adipose tissue depots which are low in AN, MAT levels are paradoxically elevated and are inversely associated with BMD. In this review, we discuss what is known about MAT in AN and the proposed hormonal determinants of this adipose tissue depot.

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Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa

Abstract: ClinicalTrials.gov identifier: NCT01642550.

Cited by 54 publications

References 34 publications

The Role of Ghrelin in Anorexia Nervosa

The Role of Ghrelin in Anorexia Nervosa

MECHANISMS IN ENDOCRINOLOGY: Anorexia nervosa and endocrinology: a clinical update

The paradox of marrow adipose tissue in anorexia nervosa

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