The Sarcopenia Study

Heart Failure Clinical Trial

Official title:

The Imaging Assessment of Sarcopenia Across the Heart Failure Spectrum

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05888688
• Other study ID #: 0916
• Status: Recruiting
• Start date: December 6, 2023
• Est. completion date: September 1, 2026

Study information

• Verified date: December 2023
• Source: University of Leicester
• Contact: Sally Utton
• Phone: 44 (0)116 204 4786
• Email: su47[@]leicester.ac.uk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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. Skeletal muscle mass, quality and body composition assessments using magnetic resonance imaging (MRI) and bioelectrical impedance analysis (BIA)

2. Skeletal muscle strength assessments (Dynamometer, FysioMeter, handgrip strength)

3. Skeletal muscle energetics assessment (31p-Spectroscopy pre/post-exercise recovery)

Researchers will compare Heart failure groups with healthy controls and adults with asymptomatic type 2 Diabetes to see if there are significant differences in the strength, mass and quality of skeletal muscle.

Description:

Heart failure is a complex condition which affects the hearts' ability to pump blood around the body properly. Due to this complexity, it often affects multiple systems in the body and can impact the quality of life. A proportion of heart failure patients also have muscle weakness, where one can feel fatigued, and weak, and may have trouble balancing and standing. To characterise muscle weakness, it is important to look at skeletal muscle mass, strength, and function. The study will focus on the prevalence of reduced muscle strength or function, using a variety of assessments within patients with heart failure. The prevalence of muscle weakness will be investigated by running assessments to look into muscle strength, a series of simple exercise tests will be run of the calf and thigh, in addition to a walking test, a balance test and a standing test to assess whole body performance. To look at the quality of skeletal muscle, a magnetic resonance imaging (MRI) and spectroscopy session will allow us to investigate the quality of the thigh muscle and the energetics in the calf. Finally, a muscle biopsy will be performed to understand differences in muscle tissue in people with different types of heart failure.

Overall, this study will provide us with unique information on skeletal muscle strength, composition and energetics within patients with heart failure, by looking at the main factors which characterise muscle weakness.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: September 1, 2026
• Est. primary completion date: September 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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.

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. Healthy volunteers

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

Exclusion criteria:

Heart failure

1. Absolute contraindication to MRI

2. Inability to walk/undertake the 6-Minute Walk Test (6MWT)

3. Neuromuscular disorders that may impact skeletal muscle assessment, such as motor neurone disease, multiple sclerosis, skeletal muscle myopathies and myositis

4. Regular or intermittent oral corticosteroid use

5. Untreated hyper or hypothyroidism

6. Heart failure-related hospitalisations in the last 3 months

Healthy volunteers

1. Previous or current signs of HF

2. Risk factors for the development of HF, such as hypertension, diabetes Mellitus or coronary artery disease

Asymptomatic Type 2 Diabetes Mellitus (T2D)

1. Angina pectoris or limiting dyspnoea (>NYHA II)

2. Major atherosclerotic disease: Symptomatic CAD, history of MI, previous revascularisation, stroke/transient ischaemic attack or symptomatic peripheral vascular disease.

3. Atrial fibrillation or flutter.

4. Moderate to severe valvular heart disease.

5. History of heart failure or cardiomyopathy.

6. Type 1 diabetes mellitus (T1DM).

7. Low fasting C-peptide levels suggestive of adult-onset T1DM.

8. Stage III-V renal disease (estimated glomerular filtration rate =30ml/min/1.73m2).

9. Absolute contraindications to MRI.

Related Conditions & MeSH terms

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

Locations

Country	Name	City	State
United Kingdom	University Hospitals of Leicester NHS Trust	Leicester	Leicestershire

Sponsors (1)

Lead Sponsor	Collaborator
University of Leicester

Country where clinical trial is conducted

United Kingdom, 

References & Publications (24)

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. — View Citation

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 Fai — View Citation

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. — View Citation

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. Erratum In: Age Ageing. 2019 Jul 1;48(4):601. — View Citation

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. — View Citation

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: 10.1 — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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):H1 — View Citation

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 — View Citation

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 Eje — View Citation

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. Erratum In: JAMA. 2020 Nov 24;324(20):2107. — View Citation

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. — View Citation

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. 20 — View Citation

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):33-4 — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. Ca — View Citation

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. — View Citation

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. 20 — View Citation

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 — View Citation

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):e00 — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	quadriceps musculoskeletal Biopsy Analysis	RNA sequencing following biopsy acquisition	Baseline
Primary	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	HF symptoms and quality of life	Minnesota Living with Heart Failure (MLWHF) questionnaire	Baseline
Secondary	Frailty assessment	Edmonton Frail scale	Baseline
Secondary	Comparison of Body composition	Bioelectrical impedance analysis (BIA) measure of Appendicular Skeletal muscle (cm^3/height) mass between patient groups	Baseline
Secondary	The difference in Muscle fat fraction (percent)	The difference in Muscle fat fraction (%) using MRI (DIXON sequence) of the quadriceps between patient groups	Baseline
Secondary	quadriceps Skeletal muscle strength (N)	The difference in quadriceps Skeletal muscle strength (N) between patient groups	Baseline
Secondary	Calf plantar flexor strength (N)	The difference in Calf plantar flexor strength (N) (c-station FysioMeter) between patient groups	Baseline
Secondary	Handgrip strength (N)	Differences in Handgrip strength (N) (Jamar Dynamometer) between patient groups	Baseline
Secondary	A comparison of post-exercise recovery metabolites	A comparison of post-exercise recovery metabolites: Phosphocreatine and inorganic phosphate ratios (PCr/Pi), and Adenosine Triphosphate (ATP) using 31p-Magnetic Resonance Spectroscopy between patient groups	Baseline
Secondary	A comparison in distance (metres) walked during 6MWT	A comparison in distance (metres) walked during Six Minute walk test (6MWT) between patient groups	Baseline
Secondary	A comparison of daily physical activity	A comparison of daily physical activity behaviours as measured by accelerometry between patient groups	Baseline
Secondary	The Short Physical Performance Battery (SPPB) performance	A comparison of lower extremity physical performance following the SPPB test between patient groups	Baseline
Secondary	Sarcopenia assessment	SARC-F (Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls) questionnaire	Baseline