{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"Research Square"}],"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T15:05:51Z","timestamp":1789830351666,"version":"4.0.1"},"posted":{"date-parts":[[2026,9,19]]},"group-title":"In Review","reference-count":44,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,8,13]]},"abstract":"<title>Abstract<\/title>\n                <p>Background\n Older adults with cirrhosis are particularly vulnerable to developing frailty with poor outcomes including increased falls, physical disability, hospitalizations, and all-cause mortality. Current management of frailty among older adults with cirrhosis is limited to general lifestyle recommendations including increased exercise and optimized diet, and few studies examining exercise interventions include patients with Child Pugh Class B or C. Whey protein and creatine are well-studied supplements commonly used to improve physical performance in athletes and have recently demonstrated positive effect in muscle mass among older adults but have not been studied in patients with cirrhosis. Therefore, we aimed to evaluate the effect of creatine\/whey protein supplementation on frailty in older adults with cirrhosis (Child Pugh Class A, B, C) engaged in Strength Training Intervention (STRIVE), a semi-supervised program practicing exercise, nutrition, and life skills.\nMethods\n This study is a randomized, placebo-controlled trial including older adults (\u2265\u200960 years) with cirrhosis evaluated at a single health center. We will recruit 200 patients informed by sample size calculations. Patients will be randomized 1:1, stratified by Child Pugh Class and gender. Participants who meet eligibility criteria will be automatically enrolled in a 2-week \u201cramp-up\u201d period to assess engagement in the exercise portion of STRIVE prior to full enrollment into the 12-week study (STRIVE with creatine\/whey protein supplementation vs placebo). We will assess health-related quality of life using Patient Reported Outcomes Measurement Information System (PROMIS-29 v 2.0), self-reported physical activity using Duke Activity Status Index (DASI), patient activation using Patient Activation Measure (PAM\u00ae), and diet quality by healthy eating index using DietID\u00ae and Automated Self-Administered Dietary Assessment Tool (ASA24). Body composition scan (BIA), liver frailty index (LFI), and morphologic measurements including waist circumference, hip circumference, midarm muscle circumference, and triceps skin fold will be measured. The primary outcome will be physical frailty (by LFI); secondary outcomes will include health-related quality of life (HrQoL), physical activity, healthy eating index, and body composition.\nDiscussion\n Our results will help inform frailty-mitigating strategies among older adults with cirrhosis that can be used for patients prior to or on the liver transplant waitlist. The addition of supplementation with creatine\/whey protein may add to the armamentarium of strategies to improve frailty within this vulnerable population.\nTrial Registration:\n NCT07029243 (Registration Date: 2025-05-15)<\/p>","DOI":"10.21203\/rs.3.rs-10695023\/v1","type":"posted-content","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:40:30Z","timestamp":1789828830000},"source":"Crossref","is-referenced-by-count":0,"title":["Strength training intervention with creatine\/whey protein supplementation vs placebo on frailty in older adults with cirrhosis (STRIVE): A Randomized Controlled Trial"],"prefix":"10.21203","author":[{"given":"Melinda","family":"Wang","sequence":"first","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothea","family":"Kent","sequence":"additional","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Pariani","sequence":"additional","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Elia","sequence":"additional","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srilakshmi","family":"Seetharaman","sequence":"additional","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Lee","sequence":"additional","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian","family":"Mansour","sequence":"additional","affiliation":[{"name":"University of Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly","family":"Mak","sequence":"additional","affiliation":[{"name":"University of Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Puneeta","family":"Tandon","sequence":"additional","affiliation":[{"name":"University of Alberta"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Lai","sequence":"additional","affiliation":[{"name":"University of California-San Francisco"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","reference":[{"issue":"11","key":"ref1","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/gerona\/glv133","article-title":"Frailty in older adults: a nationally representative profile in the United States","volume":"70","author":"Bandeen-Roche K","year":"2015","unstructured":"Bandeen-Roche K, Seplaki CL, Huang J, Buta B, Kalyani RR, Varadhan R, et al. 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