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Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa: A Randomized Clinical Trial.

ABSTRACT: OBJECTIVE:To assess the effects of relamorelin-an agonist of the appetite-stimulating hormone ghrelin, which has effects on gastric emptying-on (1) weight gain and (2) gastric emptying in women with anorexia nervosa. METHODS:In a randomized, double-blind, placebo-controlled design, the effects of the ghrelin agonist relamorelin were studied in 22 outpatient women with anorexia nervosa, diagnosed using DSM-5 criteria. The study was conducted at the Massachusetts General Hospital Clinical Research Center between March 11, 2013, and February 26, 2015. Ten participants were randomly assigned to relamorelin 100 ?g subcutaneously daily (mean ± SEM age: 28.9 ± 2.4 y), and 12 were randomly assigned to placebo (28.9 ± 1.9 y). We measured changes in weight and gastric emptying time using a gastric emptying breath test (GEBT) for relamorelin versus placebo after 4 weeks of treatment. RESULTS:At baseline, subjects did not differ in weight, plasma ghrelin levels, or gastric emptying time. Three subjects randomized to relamorelin stopped use of the study medication due to reported feelings of increased hunger. After 4 weeks, there was a trend toward an increase in weight in participants randomized to relamorelin (mean ± SEM change: 0.86 ± 0.40 kg) compared to placebo (0.04 ± 0.28 kg; P = .07), and gastric emptying time was significantly shorter in patients taking relamorelin (median [interquartile range]: 58.0 [51.0, 78.0] minutes) compared to placebo (85.0 [75.8,100.5] minutes; P = .03). CONCLUSIONS:Treatment with a ghrelin agonist in women with anorexia nervosa significantly decreases gastric emptying time, leads to a trend in weight gain after only 4 weeks, and is well-tolerated. Further study is necessary to determine the long-term safety and efficacy of a ghrelin agonist in the treatment of anorexia nervosa. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01642550.

SUBMITTER: Fazeli PK

PROVIDER: S-EPMC6908430 | biostudies-literature | 2018 Jan/Feb

REPOSITORIES: biostudies-literature

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Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa: A Randomized Clinical Trial.

Fazeli Pouneh K PK Lawson Elizabeth A EA Faje Alexander T AT Eddy Kamryn T KT Lee Hang H Fiedorek Fred T FT Breggia Anne A Gaal Ildiko M IM DeSanti Rebecca R Klibanski Anne A

The Journal of clinical psychiatry 20180101 1

<h4>Objective</h4>To assess the effects of relamorelin-an agonist of the appetite-stimulating hormone ghrelin, which has effects on gastric emptying-on (1) weight gain and (2) gastric emptying in women with anorexia nervosa.<h4>Methods</h4>In a randomized, double-blind, placebo-controlled design, the effects of the ghrelin agonist relamorelin were studied in 22 outpatient women with anorexia nervosa, diagnosed using DSM-5 criteria. The study was conducted at the Massachusetts General Hospital Cl ...[more]

PMID: 29325236

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Project description:BackgroundAnorexia nervosa is a complex psychiatric illness that includes severe low body weight with cognitive distortions and altered eating behaviors. Brain structures, including cortical thicknesses in many regions, are reduced in underweight patients who are acutely ill with anorexia nervosa. However, few studies have examined adult outpatients in the process of recovering from anorexia nervosa. Evaluating neurobiological problems at different physiological stages of anorexia nervosa may facilitate our understanding of the recovery process.MethodsMagnetic resonance imaging (MRI) images from 37 partially weight-restored women with anorexia nervosa (pwAN), 32 women with a history of anorexia nervosa maintaining weight restoration (wrAN), and 41 healthy control women were analyzed using FreeSurfer. Group differences in brain structure, including cortical thickness, areas, and volumes, were compared using a series of factorial f-tests, including age as a covariate, and correcting for multiple comparisons with the False Discovery Rate method.ResultsThe pwAN and wrAN cohorts differed from each other in body mass index, eating disorder symptoms, and social problem solving orientations, but not depression or self-esteem. Relative to the HC cohort, eight cortical thicknesses were thinner for the pwAN cohort; these regions were predominately right-sided and in the cingulate and frontal lobe. One of these regions, the right pars orbitalis, was also thinner for the wrAN cohort. One region, the right parahippocampal gyrus, was thicker in the pwAN cohort. One volume, the right cerebellar white matter, was reduced in the pwAN cohort. There were no differences in global white matter, gray matter, or subcortical volumes across the cohorts.ConclusionsMany regional structural differences were observed in the pwAN cohort with minimal differences in the wrAN cohort. These data support a treatment focus on achieving and sustaining full weight restoration to mitigate possible neurobiological sequela of AN. In addition, the regions showing cortical thinning are similar to structural changes reported elsewhere for suicide attempts, anxiety disorders, and autistic spectrum disorder. Understanding how brain structure and function are related to clinical symptoms expressed during the course of recovering from AN is needed.

Project description:IntroductionDisruptions in homeostatic and hedonic food motivation are proposed to underlie anorexia nervosa (AN) and atypical AN, restrictive eating disorders which commonly onset in puberty. Ghrelin, a neuroprotective hormone that drives hedonic eating is increased in AN and is expressed in the hippocampus. White matter (WM) undergoes significant change during puberty in regions involved in food motivation, particularly WM tracts connected with the hippocampus. The association between ghrelin and WM region of interest (ROI) with hippocampal connections in restrictive eating disorders, particularly in adolescence during key neurodevelopmental growth, is unknown.MethodsWe evaluated fasting plasma ghrelin and WM microstructure (measured by free-water corrected fractional anisotropy (FA-t)) in WM ROIs with hippocampal connections - the fornix and the hippocampal portion of the cingulum - in 56 adolescent females (age range: 11.9 - 22.1 y; mean: 19.0 y) with low-weight eating disorders including AN and atypical AN (N = 36) and healthy controls (N = 20).ResultsFA-t in the fornix or hippocampal portion of the fornix did not differ between groups. Ghrelin was higher in AN/atypical AN vs. HC and was positively correlated with puberty stage in the AN/atypical AN group, but not the HC group. The correlation between ghrelin and FA-t in the fornix was significantly different in females with AN/atypical AN compared to controls. In AN/atypical AN, pubertal stage moderated the relation between fasting plasma ghrelin and FA-t in the fornix: higher fasting ghrelin was associated with lower FA-t in the fornix in late-post-puberty, but was not associated with FA-t in the early to mid stages of puberty.ConclusionsIn post-pubertal females with low-weight AN/atypical AN, higher levels of ghrelin are associated with lower FA-t in the fornix. This relationship is not evident in the early to mid stages of puberty in AN/atypical AN or in HC, and may reflect a lack of possible neuroprotective effects of ghrelin in late-post puberty only. Understanding the effects of ghrelin on WM microstructure longitudinally and following recovery from AN/Atypical AN and how this differs across pubertal stages will be an important next step. These findings could ultimately inform treatment staging and aid in diagnosis and detection of AN/atypical AN.

Project description:Reduced Environmental Stimulation Therapy (REST) alters the balance of sensory input to the nervous system by systematically attenuating sensory signals from visual, auditory, thermal, tactile, vestibular, and proprioceptive channels. Previous research from our group has shown that REST via floatation acutely reduces anxiety and blood pressure (BP) while simultaneously heightening interoceptive awareness in clinically anxious populations. Anorexia nervosa (AN) is an eating disorder characterized by elevated anxiety, distorted body representation, and abnormal interoception, raising the question of whether REST might positively impact these symptoms. However, this approach has never been studied in eating disorders, and it is unknown whether exposure to floatation REST might worsen AN symptoms. To examine these possibilities, we conducted an open-label study to investigate the safety and tolerability of REST in AN. We also explored the acute impact of REST on BP, affective symptoms, body image disturbance, and interoception. Twenty-one partially weight-restored AN outpatients completed a protocol involving four sequential sessions of REST: reclining in a zero-gravity chair, floating in an open pool, and two sessions of floating in an enclosed pool. All sessions were 90 min, approximately 1 week apart. We measured orthostatic BP before and immediately after each session (primary outcome), in addition to collecting BP readings every 10 min during the session using a wireless waterproof system as a secondary outcome measure. Each participant's affective state, awareness of interoceptive sensations, and body image were assessed before and after every session (exploratory outcomes). There was no evidence of orthostatic hypotension following floating, and no adverse events (primary outcome). Secondary analyses revealed that REST induced statistically significant reductions in BP (p < 0.001; Cohen's d, 0.2-0.5), anxiety (p < 0.001; Cohen's d, >1) and negative affect (p < 0.01; Cohen's d, >0.5), heightened awareness of cardiorespiratory (p < 0.01; Cohen's d, 0.2-0.5) but not gastrointestinal sensations, and reduced body image dissatisfaction (p < 0.001; Cohen's d, >0.5). The findings from this initial trial suggest that individuals with AN can safely tolerate the physical effects of REST via floatation. Future randomized controlled trials will need to investigate whether these initial observations of improved anxiety, interoception, and body image disturbance occur in acutely ill AN populations. Clinical Trial Registration:ClinicalTrials.gov; Identifier: NCT02801084 (April 01, 2016).

Project description:UnlabelledResearch on treatments in anorexia nervosa (AN) is scarce. Although most of the therapeutic programs used in 'real world practice' in AN treatment resort to multidisciplinary approaches, they have rarely been evaluated.ObjectiveTo compare two multidimensional post-hospitalization outpatients treatment programs for adolescents with severe AN: Treatment as Usual (TAU) versus this treatment plus family therapy (TAU+FT).MethodSixty female AN adolescents, aged 13 to 19 years, were included in a randomized parallel controlled trial conducted from 1999 to 2002 for the recruitment, and until 2004 for the 18 months follow-up. Allocation to one of the two treatment groups (30 in each arm) was randomised. The TAU program included sessions for the patient alone as well as sessions with a psychiatrist for the patient and her parents. The TAU+FT program was identical to the usual one but also included family therapy sessions targeting intra-familial dynamics, but not eating disorder symptoms. The main Outcome Measure was the Morgan and Russell outcome category (Good or Intermediate versus Poor outcome). Secondary outcome indicators included AN symptoms or their consequences (eating symptoms, body mass index, amenorrhea, number of hospitalizations in the course of follow-up, social adjustment). The evaluators, but not participants, were blind to randomization.ResultsAt 18 months follow-up, we found a significant group effect for the Morgan and Russell outcome category in favor of the program with family therapy (Intention-to-treat: TAU+FT :12/30 (40%); TAU : 5/29 (17.2%) p?=?0.05; Per Protocol analysis: respectively 12/26 (46.2%); 4/27 (14.8%), p?=?0.01). Similar group effects were observed in terms of achievement of a healthy weight (i.e., BMI?10(th) percentile) and menstrual status.ConclusionsAdding family therapy sessions, focusing on intra-familial dynamics rather than eating symptomatology, to a multidimensional program improves treatment effectiveness in girls with severe AN.Trial registrationControlled-trials.com ISRCTN71142875.

Dataset Information

Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa: A Randomized Clinical Trial.

Publications

Treatment With a Ghrelin Agonist in Outpatient Women With Anorexia Nervosa: A Randomized Clinical Trial.

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