Evidence map›Paper›PMID 42821228›Full record

ArticleAdvances in therapy2026

Measuring Hunger Severity in Rare MC4R Pathway Diseases: Development and Psychometric Evaluation of the Most Hunger Item.

Karine Clément, Christian L Roth, Peter Kühnen, Andrea M Haqq, Usha G Mallya, Claire Ervin, Lindsey Norcross, Sakshi Bhargava, Jesús Argente, Jennifer L Miller

4 registry-linked trialsAbstract read
PubMed Publisher
In one paragraph

Article in Advances in therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02896192 phase3completednot on this map

An Open-Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of Setmelanotide (RM-493), a Melanocortin 4 Receptor (MC4R) Agonist, in Early Onset POMC Deficiency Obesity Due to Bi-Allelic Loss-of-Function POMC or PCSK1 Genetic Mutation

TypeinterventionalSponsorRhythm Pharmaceuticals, Inc.Ran2017 to 2020Enrolled15ConditionsPro-opiomelanocortin (POMC) Deficiency ObesityArmsSetmelanotide, Placebo
NCT03287960 phase3completednot on this map

An Open Label, 1-Year Trial, Including a Double-Blind Placebo-Controlled Withdrawal Period, of Setmelanotide (RM-493), a Melanocortin 4 Receptor (MC4R) Agonist, in Leptin Receptor (LEPR) Deficiency Obesity Due to Bi-Allelic Loss-of-Function LEPR Genetic Mutation

TypeinterventionalSponsorRhythm Pharmaceuticals, Inc.Ran2018 to 2020Enrolled15ConditionsLeptin Receptor Deficiency ObesityArmsSetmelanotide, Placebo
NCT03746522 phase3completednot on this map

A Phase 3 Trial of Setmelanotide (RM-493), a Melanocortin-4 Receptor (MC4R) Agonist, in Bardet-Biedl Syndrome (BBS) and Alström Syndrome (AS) Patients With Moderate to Severe Obesity

TypeinterventionalSponsorRhythm Pharmaceuticals, Inc.Ran2018 to 2021Enrolled52ConditionsBardet Biedl Syndrome (BBS), Alström Syndrome (AS)ArmsSetmelanotide, Placebo
NCT05774756 phase3active not recruitingnot on this map

A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic Obesity

TypeinterventionalSponsorRhythm Pharmaceuticals, Inc.Ran2023 to 2027Enrolled143ConditionsHypothalamic ObesityArmsSetmelanotide, Placebo
3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Karine ClémentNutrition and Obesities: Systemic Approaches, NutriOmics Research Group, INSERM, Sorbonne Université, Paris, France.
Christian L RothSeattle Children's Research Institute, Seattle, WA, USA.
Peter KühnenDepartment of Pediatric Endocrinology and Diabetology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Andrea M HaqqDepartment of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB, Canada.
Usha G MallyaRhythm Pharmaceuticals, Inc., Boston, MA, USA.
Claire ErvinRTI Health Solutions, 3040 East Cornwallis Road, PO Box 12194, Durham, NC, 27713, USA. cervin@rti.org.ORCID http://orcid.org/0000-0003-2546-8980
Lindsey NorcrossRTI Health Solutions, 3040 East Cornwallis Road, PO Box 12194, Durham, NC, 27713, USA.
Sakshi BhargavaRTI Health Solutions, 3040 East Cornwallis Road, PO Box 12194, Durham, NC, 27713, USA.
Jesús ArgenteDepartment of Endocrinology, Hospital Infantil Universitario Niño Jesús, Instituto de Investigación La Princesa, Madrid, Spain.
Jennifer L MillerPediatric Endocrinology, Department of Pediatrics, College of Medicine, University of Florida, Gainesville, FL, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionLeptin receptor (LEPR) deficiency, pro-opiomelanocortin (POMC) deficiency, Bardet-Biedl syndrome (BBS), and acquired hypothalamic obesity (HO) are diseases of the melanocortin 4 receptor (MC4R) pathway that often lead to insatiable hunger and severe obesity. As targeted treatments, such as setmelanotide, emerge for these diseases, it is critical to understand treatment benefit from patients' perspectives. This study describes the development and psychometric evaluation of the Most Hunger item, a patient-reported outcome (PRO) measure assessing hunger in patients with MC4R pathway diseases.

methodsThe content validity and appropriateness of the Most Hunger item were evaluated across three separate qualitative interview studies with individuals with LEPR or POMC deficiency, BBS, and acquired HO. Semistructured interviews were conducted. The psychometric evaluation assessed the reliability, validity, responsiveness, and meaningful within-patient change (MWPC) thresholds of the Most Hunger item using responses collected during phase 3 trials of setmelanotide from participants aged ≥12 years with LEPR or POMC deficiency, BBS, or acquired HO.

resultsQualitative interview participants understood the Most Hunger item and could rate their hunger using the item. Hunger scores and patient experiences with hunger were consistent across the three patient populations; patients described an unrelenting hunger prior to treatment and an impactful reduction in hunger post treatment. The Most Hunger item had moderate to good test-retest reliability, and convergent correlations supported its validity. Among patients with LEPR or POMC deficiency, BBS, or acquired HO, MWPC thresholds for Most Hunger (0-10 response scale) were estimated as 1.5-2.6, 0.95-1.6, and 2.4-3.7, respectively.

conclusionIndividuals with these distinct MC4R pathway diseases experience similar and high levels of hunger severity, with behaviors consistent with hyperphagia. The Most Hunger item is a fit-for-purpose PRO measure of hunger to assess treatment benefit in patients aged ≥12 years with LEPR or POMC deficiency, BBS, or acquired HO. TRIAL REGISTRATIONS: ClinicalTrials.gov identifiers, NCT03287960, NCT02896192, NCT03746522, and NCT05774756.

Indexed as

Acquired hypothalamic obesityBardet–Biedl syndromeHyperphagiaLeptin receptorMelanocortin receptor pathway diseasesMost hunger itemPatient-reported outcomePro-opiomelanocortinPsychometric evaluationSetmelanotide

Identifiers

PMID42821228

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.