The Sarcopenia Study

NCT05888688 | Recruiting

• 1 other identifier: 0916
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this cross-sectional study is to investigate the prevalence of sarcopenia in patients with Heart Failure. The main question it aims to answer is: Whether there is a difference in the prevalence of sarcopenia across the spectrum of HFpEF (Heart failure with preserved ejection fraction) and HFrEF (heart failure with reduced ejection fraction). This is an observational study. The participant population involves patients with heart failure with preserved ejection fraction and heart failure with reduced ejection fraction. Healthy volunteers will be recruited as controls in addition to adults with asymptomatic Type 2 Diabetes. Participants will undergo the following:

1. 1.Skeletal muscle mass, quality and body composition assessments using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA)
2. 2.Skeletal muscle strength assessments (Dynamometer, FysioMeter, handgrip strength)
3. 3.Skeletal muscle energetics assessment (31p-Spectroscopy pre/post-exercise recovery)

Conditions

Heart Failure; Sarcopenia; Heart Failure With Reduced Ejection Fraction; Heart Failure With Preserved Ejection Fraction; Type 2 Diabetes; Frailty

Keywords

Heart Failure; Sarcopenia; Frailty; Skeletal Muscle; Magnetic Resonance Imaging; 31-Phosphorous magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (1)

• Volumetric quadriceps skeletal muscle mass (cm^3)

  A comparison of volumetric quadriceps skeletal muscle mass (cm3) using MRI between HFpEF and HFrEF patients

  Through study completion, an average of 3 years

Secondary Outcomes (12)

• HF symptoms and quality of life

  Baseline

• Frailty assessment

  Baseline

• Comparison of Body composition

  Baseline

• The difference in Muscle fat fraction (percent)

  Baseline

• quadriceps Skeletal muscle strength (N)

  Baseline

Other Outcomes (1)

• quadriceps musculoskeletal Biopsy Analysis

  Baseline

Study Arms (4)

patients with Heart Failure with Preserved Ejection Fraction (HFpEF)

Heart Failure (HF) Patients: Stage A/B HFpEF 1. Established clinical diagnosis of HFpEF (EF\>50%) 2. Clinically stable for ≥ 3 months (no admissions to hospital) 3. Age ≥65 4. Willing to provide written consent for participation in the study.

patients with Heart Failure with Reduced Ejection Fraction (HFrEF)

HF Patients: Stage C/D HFpEF and HFrEF 1. Established clinical diagnosis of HFpEF (EF\>50%) OR HFrEF (EF\<40%) 2. Clinically stable for ≥ 3 months (no admissions to hospital) 3. Age ≥65 4. Willing to provide written consent for participation in the study.

Asymptomatic T2D

1. Male or female, aged ≥18 and ≤75 years. 2. Diagnosis of stable T2D (determined by i) formal diagnosis in primary care physician case records, ii) a record of diagnostic oral glucose tolerance test OR glycated haemoglobin level ≥6.5%).

Healthy Volunteers

1. Age \>18 2. Able to provide written informed consent

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Four groups of subjects will be recruited, subjects with HFpEF, HFrEF, asymptomatic T2D and metabolically healthy non-diabetic controls. The ongoing studies will allow the co-enrolment of participants. They will be recruited to match age, sex and ethnicity as closely as possible to the HF participants.

You may qualify if:

• Heart Failure (HF) Patients: Stage A/B HFpEF
• Established clinical diagnosis of HFpEF (EF\>50%)
• Clinically stable for ≥ 3 months (no admissions to hospital)
• Age ≥65
• Willing to provide written consent for participation in the study.
• HF Patients: Stage C/D HFpEF and HFrEF
• Established clinical diagnosis of HFpEF (EF\>50%) OR HFrEF (EF\<40%)
• Clinically stable for ≥ 3 months (no admissions to hospital)
• Age ≥65
• Willing to provide written consent for participation in the study. Healthy volunteers
• \. Age \>18 2. Able to provide written informed consent Asymptomatic T2D
• Male or female, aged ≥18 and ≤75 years.
• Diagnosis of stable T2D (determined by i) formal diagnosis in primary care physician case records, ii) a record of diagnostic oral glucose tolerance test OR glycated haemoglobin level ≥6.5%).

You may not qualify if:

• Heart failure
• Absolute contraindication to MRI
• Inability to walk/undertake the 6-Minute Walk Test (6MWT)
• Neuromuscular disorders that may impact skeletal muscle assessment, such as motor neurone disease, multiple sclerosis, skeletal muscle myopathies and myositis
• Regular or intermittent oral corticosteroid use
• Untreated hyper or hypothyroidism
• Heart failure-related hospitalisations in the last 3 months
• Healthy volunteers
• Previous or current signs of HF
• Risk factors for the development of HF, such as hypertension, diabetes Mellitus or coronary artery disease
• Asymptomatic Type 2 Diabetes Mellitus (T2D)
• Angina pectoris or limiting dyspnoea (\>NYHA II)
• Major atherosclerotic disease: Symptomatic CAD, history of MI, previous revascularisation, stroke/transient ischaemic attack or symptomatic peripheral vascular disease.
• Atrial fibrillation or flutter.
• Moderate to severe valvular heart disease.

Sponsors & Collaborators

• University of Leicester: lead

Study Sites (1)

University Hospitals of Leicester NHS Trust

Leicester, Leicestershire, LE1 5WW, United Kingdom

RECRUITING

Related Publications (24)

• Redfield MM, Borlaug BA. Heart Failure With Preserved Ejection Fraction: A Review. JAMA. 2023 Mar 14;329(10):827-838. doi: 10.1001/jama.2023.2020.

  PMID: 36917048 BACKGROUND

• Murphy SP, Ibrahim NE, Januzzi JL Jr. Heart Failure With Reduced Ejection Fraction: A Review. JAMA. 2020 Aug 4;324(5):488-504. doi: 10.1001/jama.2020.10262.

  PMID: 32749493 BACKGROUND

• Del Buono MG, Arena R, Borlaug BA, Carbone S, Canada JM, Kirkman DL, Garten R, Rodriguez-Miguelez P, Guazzi M, Lavie CJ, Abbate A. Exercise Intolerance in Patients With Heart Failure: JACC State-of-the-Art Review. J Am Coll Cardiol. 2019 May 7;73(17):2209-2225. doi: 10.1016/j.jacc.2019.01.072.

  PMID: 31047010 BACKGROUND

• Pandey A, Shah SJ, Butler J, Kellogg DL Jr, Lewis GD, Forman DE, Mentz RJ, Borlaug BA, Simon MA, Chirinos JA, Fielding RA, Volpi E, Molina AJA, Haykowsky MJ, Sam F, Goodpaster BH, Bertoni AG, Justice JN, White JP, Ding J, Hummel SL, LeBrasseur NK, Taffet GE, Pipinos II, Kitzman D. Exercise Intolerance in Older Adults With Heart Failure With Preserved Ejection Fraction: JACC State-of-the-Art Review. J Am Coll Cardiol. 2021 Sep 14;78(11):1166-1187. doi: 10.1016/j.jacc.2021.07.014.

  PMID: 34503685 BACKGROUND

• Salmon T, Essa H, Tajik B, Isanejad M, Akpan A, Sankaranarayanan R. The Impact of Frailty and Comorbidities on Heart Failure Outcomes. Card Fail Rev. 2022 Mar 21;8:e07. doi: 10.15420/cfr.2021.29. eCollection 2022 Jan.

  PMID: 35399550 BACKGROUND

• Cruz-Jentoft AJ, Bahat G, Bauer J, Boirie Y, Bruyere O, Cederholm T, Cooper C, Landi F, Rolland Y, Sayer AA, Schneider SM, Sieber CC, Topinkova E, Vandewoude M, Visser M, Zamboni M; Writing Group for the European Working Group on Sarcopenia in Older People 2 (EWGSOP2), and the Extended Group for EWGSOP2. Sarcopenia: revised European consensus on definition and diagnosis. Age Ageing. 2019 Jan 1;48(1):16-31. doi: 10.1093/ageing/afy169.

  PMID: 30312372 BACKGROUND

• Tucker WJ, Haykowsky MJ, Seo Y, Stehling E, Forman DE. Impaired Exercise Tolerance in Heart Failure: Role of Skeletal Muscle Morphology and Function. Curr Heart Fail Rep. 2018 Dec;15(6):323-331. doi: 10.1007/s11897-018-0408-6.

  PMID: 30178183 BACKGROUND

• Uchmanowicz I, Mlynarska A, Lisiak M, Kaluzna-Oleksy M, Wleklik M, Chudiak A, Dudek M, Migaj J, Hinterbuchner L, Gobbens R. Heart Failure and Problems with Frailty Syndrome: Why it is Time to Care About Frailty Syndrome in Heart Failure. Card Fail Rev. 2019 Feb;5(1):37-43. doi: 10.15420/cfr.2018.37.1.

  PMID: 30847244 RESULT

• Kitzman DW, Nicklas B, Kraus WE, Lyles MF, Eggebeen J, Morgan TM, Haykowsky M. Skeletal muscle abnormalities and exercise intolerance in older patients with heart failure and preserved ejection fraction. Am J Physiol Heart Circ Physiol. 2014 May;306(9):H1364-70. doi: 10.1152/ajpheart.00004.2014. Epub 2014 Mar 21.

  PMID: 24658015 RESULT

• Kirkman DL, Bohmke N, Billingsley HE, Carbone S. Sarcopenic Obesity in Heart Failure With Preserved Ejection Fraction. Front Endocrinol (Lausanne). 2020 Sep 30;11:558271. doi: 10.3389/fendo.2020.558271. eCollection 2020.

  PMID: 33117276 RESULT

• Bilak JM, Gulsin GS, McCann GP. Cardiovascular and systemic determinants of exercise capacity in people with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2021 Jan 27;12:2042018820980235. doi: 10.1177/2042018820980235. eCollection 2021.

  PMID: 33552463 RESULT

• Kinugasa Y, Yamamoto K. The challenge of frailty and sarcopenia in heart failure with preserved ejection fraction. Heart. 2017 Feb;103(3):184-189. doi: 10.1136/heartjnl-2016-309995. Epub 2016 Dec 9.

  PMID: 27940967 RESULT

• Pandey A, Parashar A, Kumbhani D, Agarwal S, Garg J, Kitzman D, Levine B, Drazner M, Berry J. Exercise training in patients with heart failure and preserved ejection fraction: meta-analysis of randomized control trials. Circ Heart Fail. 2015 Jan;8(1):33-40. doi: 10.1161/CIRCHEARTFAILURE.114.001615. Epub 2014 Nov 16.

  PMID: 25399909 RESULT

• Hamada T, Kubo T, Kawai K, Nakaoka Y, Yabe T, Furuno T, Yamada E, Kitaoka H; Kochi YOSACOI study. Clinical characteristics and frailty status in heart failure with preserved vs. reduced ejection fraction. ESC Heart Fail. 2022 Jun;9(3):1853-1863. doi: 10.1002/ehf2.13885. Epub 2022 Mar 30.

  PMID: 35355441 RESULT

• Visser M, Goodpaster BH, Kritchevsky SB, Newman AB, Nevitt M, Rubin SM, Simonsick EM, Harris TB. Muscle mass, muscle strength, and muscle fat infiltration as predictors of incident mobility limitations in well-functioning older persons. J Gerontol A Biol Sci Med Sci. 2005 Mar;60(3):324-33. doi: 10.1093/gerona/60.3.324.

  PMID: 15860469 RESULT

• Oba H, Matsui Y, Arai H, Watanabe T, Iida H, Mizuno T, Yamashita S, Ishizuka S, Suzuki Y, Hiraiwa H, Imagama S. Evaluation of muscle quality and quantity for the assessment of sarcopenia using mid-thigh computed tomography: a cohort study. BMC Geriatr. 2021 Apr 13;21(1):239. doi: 10.1186/s12877-021-02187-w.

  PMID: 33849469 RESULT

• Chianca V, Albano D, Messina C, Gitto S, Ruffo G, Guarino S, Del Grande F, Sconfienza LM. Sarcopenia: imaging assessment and clinical application. Abdom Radiol (NY). 2022 Sep;47(9):3205-3216. doi: 10.1007/s00261-021-03294-3. Epub 2021 Oct 23.

  PMID: 34687326 RESULT

• Weiss K, Schar M, Panjrath GS, Zhang Y, Sharma K, Bottomley PA, Golozar A, Steinberg A, Gerstenblith G, Russell SD, Weiss RG. Fatigability, Exercise Intolerance, and Abnormal Skeletal Muscle Energetics in Heart Failure. Circ Heart Fail. 2017 Jul;10(7):e004129. doi: 10.1161/CIRCHEARTFAILURE.117.004129.

  PMID: 28705910 RESULT

• Kitzman DW, Brubaker P, Morgan T, Haykowsky M, Hundley G, Kraus WE, Eggebeen J, Nicklas BJ. Effect of Caloric Restriction or Aerobic Exercise Training on Peak Oxygen Consumption and Quality of Life in Obese Older Patients With Heart Failure With Preserved Ejection Fraction: A Randomized Clinical Trial. JAMA. 2016 Jan 5;315(1):36-46. doi: 10.1001/jama.2015.17346.

  PMID: 26746456 RESULT

• Molina AJ, Bharadwaj MS, Van Horn C, Nicklas BJ, Lyles MF, Eggebeen J, Haykowsky MJ, Brubaker PH, Kitzman DW. Skeletal Muscle Mitochondrial Content, Oxidative Capacity, and Mfn2 Expression Are Reduced in Older Patients With Heart Failure and Preserved Ejection Fraction and Are Related to Exercise Intolerance. JACC Heart Fail. 2016 Aug;4(8):636-45. doi: 10.1016/j.jchf.2016.03.011. Epub 2016 May 11.

  PMID: 27179829 RESULT

• O'Neill S, Weeks A, Norgaard JE, Jorgensen MG. Validity and intrarater reliability of a novel device for assessing Plantar flexor strength. PLoS One. 2023 Mar 31;18(3):e0282395. doi: 10.1371/journal.pone.0282395. eCollection 2023.

  PMID: 37000780 RESULT

• Brubaker PH, Nicklas BJ, Houston DK, Hundley WG, Chen H, Molina AJA, Lyles WM, Nelson B, Upadhya B, Newland R, Kitzman DW. A Randomized, Controlled Trial of Resistance Training Added to Caloric Restriction Plus Aerobic Exercise Training in Obese Heart Failure With Preserved Ejection Fraction. Circ Heart Fail. 2023 Feb;16(2):e010161. doi: 10.1161/CIRCHEARTFAILURE.122.010161. Epub 2022 Oct 31.

  PMID: 36314122 RESULT

• Konishi M, Kagiyama N, Kamiya K, Saito H, Saito K, Ogasahara Y, Maekawa E, Misumi T, Kitai T, Iwata K, Jujo K, Wada H, Kasai T, Nagamatsu H, Ozawa T, Izawa K, Yamamoto S, Aizawa N, Makino A, Oka K, Momomura SI, Matsue Y. Impact of sarcopenia on prognosis in patients with heart failure with reduced and preserved ejection fraction. Eur J Prev Cardiol. 2021 Aug 9;28(9):1022-1029. doi: 10.1093/eurjpc/zwaa117.

  PMID: 33624112 RESULT

• Sugita Y, Ito K, Yoshioka Y, Sakai S. Association of complication of type 2 diabetes mellitus with hemodynamics and exercise capacity in patients with heart failure with preserved ejection fraction: a case-control study in individuals aged 65-80 years. Cardiovasc Diabetol. 2023 Apr 28;22(1):97. doi: 10.1186/s12933-023-01835-2.

  PMID: 37118820 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Skeletal muscle biopsy obtained from the thigh.

MeSH Terms

Conditions

Heart Failure; Sarcopenia; Diabetes Mellitus, Type 2; Frailty

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Pathologic Processes

Study Officials

• Gerry McCann, BSc, MB, ChB, MRCP, MD

  University of Leicester (UoL)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sally Utton

CONTACT

44 (0)116 204 4786; su47@leicester.ac.uk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 15, 2023
• First Posted: June 5, 2023
• Study Start: December 6, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

GB (1)