Study to Weigh the Effect of Exercise Training on BONE (SWEET-BONE) Quality and Strength in Type 2 Diabetes

NCT02421393 | Completed

• 1 other identifier: MFA-04
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Type 2 diabetes mellitus (T2DM) is associated with increased fracture risk despite normal to increased bone mass, thus suggesting poor bone quality. This study is aimed at weighing the effect of an exercise intervention program on parameters of bone quality in patients with type 2 diabetes mellitus. Two hundred patients with T2DM will be randomized to supervised exercise training on top of standard care (exercise, EXE, group; n=100) versus standard care (control, CON, group; n=100) for 24 months.

Conditions

Type 2 Diabetes

Keywords

Bone quality; Bone strength; Fractures; Muscle strength; Gait and balance; Musculo-skeletal symptoms; Falls

Outcome Measures

Primary Outcomes (1)

• Effect of intervention on bone quality (trabecular bone score)

  Effect of exercise intervention training on trabecular bone score (TBS)

  2 years

Secondary Outcomes (10)

• Effect of intervention on other measures of bone quality (composite)

  2 years

• Effect of intervention on bone mass (dual-energy X-ray absorptiometry)

  2 years

• Effect of intervention on bone metabolism (composite)

  2 years

• Effect of intervention on body composition (total body dual-energy X-ray absorptiometry )

  2 years

• Effect of intervention on muscle strength (dynamometry)

  2 years

Other Outcomes (5)

• Effect of intervention on quality of life (QoL) (SF-36 questionnaire)

  2 years

• Effect of intervention on cardiorespiratory fitness (VO2max)

  2 years

• Effect of intervention on flexibility (bending test)

  2 years

Study Arms (2)

Exercise

EXPERIMENTAL

Supervised exercise training on top of standard care (exercise, EXE, group; n=100)

Other: supervised exercise training

Control

NO INTERVENTION

Standard care including advises to maintain a physically active lifestyle, according to current guidelines, by performing any type of commuting, occupational, home and and leisure-time physical activity (PA) (control, CON, group; n=100).

Interventions

supervised exercise training OTHER

Two weekly sessions of 75 min each, supervised by an exercise specialist in a dedicated gym facility. Each session will include: 5 min of warm up; 20 min of aerobic training using treadmill; 15 min of resistance training of muscle groups of skeletal sites of fragility fractures; 15 min of "weight bearing" exercises using weighted vests; 8 min of core stability training; 8 min of balance training; and 4 min of flexibility training. Weighted vest worn also during aerobic training and any occupational, home and leisure-time physical activity.

Exercise

Eligibility Criteria

• Age: 65 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• diabetes duration \>5-year
• sedentary lifestyle (i.e. more than 8 hours/day spent in any waking behavior characterized by an energy expenditure ≤1.5 metabolic equivalents \[METs\] while in a sitting or reclining posture) from at least 6 months;
• physically inactivity (i.e. insufficient amounts of physical activity \[PA\] according to current guidelines) from at least 6 months;
• body mass index (BMI) 27-40 kg/m2;
• ability to walk 1.6 Km without assistance;
• a Short Battery Performance Test score ranging from 4 to 9;
• eligibility after cardiologic evaluation.

You may not qualify if:

• any condition limiting participation in a clinical trial, including psychiatric disorders or hospitalization for depression in the past 6 months;
• any condition limiting PA/exercise, including musculoskeletal disorders or deformities, central nervous system dysfunction such as hemiparesis, myelopathies, cerebral ataxia, vestibular dysfunction, and postural hypotension (i.e. a fall of \>20 mmHg of systolic or \>10 mmHg of diastolic blood pressure when changing position);
• cancer and other life-expectancy limiting conditions;
• recent major acute cardiovascular event, including heart attack, stroke/transient ischemic attack(s), revascularization procedure, or participation in a cardiac rehabilitation program within the past three months, or documented history of pulmonary embolism in the past six months;
• pre-proliferative and proliferative retinopathy;
• macroalbuminuria and/or estimated glomerular filtration rate (eGFR) \<45 ml/min/1.73 m2;
• ankle/brachial index (ABI) \<0.9;
• severe motor and sensory neuropathy;
• diabetic foot with history of ulcer;
• hemoglobin (Hb) A1c \>9.0%;
• blood pressure (BP) \>150/90 mmHg;
• vitamin D \<10 ng/ml;
• treatment with anti-fracturative agents, estrogens, aromatase inhibitors, testosterone, corticosteroids and/or glitazon;
• previous documented non-traumatic fractures,
• total spine deformity index (SDI) \>3 (and \>1 in a single vertebra);

Sponsors & Collaborators

• Metabolic Fitness Association, Italy: lead
• University of Roma La Sapienza: collaborator
• S. Andrea Hospital: collaborator

Study Sites (1)

S. Andrea Hospital

Rome, RM, 00189, Italy

Location

Related Publications (27)

• Balducci S, Zanuso S, Cardelli P, Salvi L, Mazzitelli G, Bazuro A, Iacobini C, Nicolucci A, Pugliese G; Italian Diabetes Exercise Study (IDES) Investigators. Changes in physical fitness predict improvements in modifiable cardiovascular risk factors independently of body weight loss in subjects with type 2 diabetes participating in the Italian Diabetes and Exercise Study (IDES). Diabetes Care. 2012 Jun;35(6):1347-54. doi: 10.2337/dc11-1859. Epub 2012 Mar 7.

  PMID: 22399699 BACKGROUND

• Balducci S, Zanuso S, Nicolucci A, De Feo P, Cavallo S, Cardelli P, Fallucca S, Alessi E, Fallucca F, Pugliese G; Italian Diabetes Exercise Study (IDES) Investigators. Effect of an intensive exercise intervention strategy on modifiable cardiovascular risk factors in subjects with type 2 diabetes mellitus: a randomized controlled trial: the Italian Diabetes and Exercise Study (IDES). Arch Intern Med. 2010 Nov 8;170(20):1794-803. doi: 10.1001/archinternmed.2010.380.

  PMID: 21059972 BACKGROUND

• Bonds DE, Larson JC, Schwartz AV, Strotmeyer ES, Robbins J, Rodriguez BL, Johnson KC, Margolis KL. Risk of fracture in women with type 2 diabetes: the Women's Health Initiative Observational Study. J Clin Endocrinol Metab. 2006 Sep;91(9):3404-10. doi: 10.1210/jc.2006-0614. Epub 2006 Jun 27.

  PMID: 16804043 BACKGROUND

• Burghardt AJ, Issever AS, Schwartz AV, Davis KA, Masharani U, Majumdar S, Link TM. High-resolution peripheral quantitative computed tomographic imaging of cortical and trabecular bone microarchitecture in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010 Nov;95(11):5045-55. doi: 10.1210/jc.2010-0226. Epub 2010 Aug 18.

  PMID: 20719835 BACKGROUND

• Carnevale V, Romagnoli E, D'Erasmo L, D'Erasmo E. Bone damage in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis. 2014 Nov;24(11):1151-7. doi: 10.1016/j.numecd.2014.06.013. Epub 2014 Jul 27.

  PMID: 25150773 BACKGROUND

• Chan MY, Frost SA, Center JR, Eisman JA, Nguyen TV. Relationship between body mass index and fracture risk is mediated by bone mineral density. J Bone Miner Res. 2014 Nov;29(11):2327-35. doi: 10.1002/jbmr.2288.

  PMID: 24862213 BACKGROUND

• Cousins JM, Petit MA, Paudel ML, Taylor BC, Hughes JM, Cauley JA, Zmuda JM, Cawthon PM, Ensrud KE; Osteoporotic Fractures in Men (MrOS) Study Group. Muscle power and physical activity are associated with bone strength in older men: The osteoporotic fractures in men study. Bone. 2010 Aug;47(2):205-11. doi: 10.1016/j.bone.2010.05.003. Epub 2010 May 11.

  PMID: 20466088 BACKGROUND

• De Laet C, Kanis JA, Oden A, Johanson H, Johnell O, Delmas P, Eisman JA, Kroger H, Fujiwara S, Garnero P, McCloskey EV, Mellstrom D, Melton LJ 3rd, Meunier PJ, Pols HA, Reeve J, Silman A, Tenenhouse A. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005 Nov;16(11):1330-8. doi: 10.1007/s00198-005-1863-y. Epub 2005 Jun 1.

  PMID: 15928804 BACKGROUND

• de Waard EA, van Geel TA, Savelberg HH, Koster A, Geusens PP, van den Bergh JP. Increased fracture risk in patients with type 2 diabetes mellitus: an overview of the underlying mechanisms and the usefulness of imaging modalities and fracture risk assessment tools. Maturitas. 2014 Nov;79(3):265-74. doi: 10.1016/j.maturitas.2014.08.003. Epub 2014 Aug 18.

  PMID: 25192916 BACKGROUND

• Dobnig H, Piswanger-Solkner JC, Roth M, Obermayer-Pietsch B, Tiran A, Strele A, Maier E, Maritschnegg P, Sieberer C, Fahrleitner-Pammer A. Type 2 diabetes mellitus in nursing home patients: effects on bone turnover, bone mass, and fracture risk. J Clin Endocrinol Metab. 2006 Sep;91(9):3355-63. doi: 10.1210/jc.2006-0460. Epub 2006 May 30.

  PMID: 16735485 BACKGROUND

• Donnelly E. Methods for assessing bone quality: a review. Clin Orthop Relat Res. 2011 Aug;469(8):2128-38. doi: 10.1007/s11999-010-1702-0.

  PMID: 21116752 BACKGROUND

• Gonnelli S, Caffarelli C, Nuti R. Obesity and fracture risk. Clin Cases Miner Bone Metab. 2014 Jan;11(1):9-14. doi: 10.11138/ccmbm/2014.11.1.009.

  PMID: 25002873 BACKGROUND

• Howe TE, Shea B, Dawson LJ, Downie F, Murray A, Ross C, Harbour RT, Caldwell LM, Creed G. Exercise for preventing and treating osteoporosis in postmenopausal women. Cochrane Database Syst Rev. 2011 Jul 6;2011(7):CD000333. doi: 10.1002/14651858.CD000333.pub2.

  PMID: 21735380 BACKGROUND

• Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007 Sep 1;166(5):495-505. doi: 10.1093/aje/kwm106. Epub 2007 Jun 16.

  PMID: 17575306 BACKGROUND

• Johansson H, Kanis JA, Oden A, McCloskey E, Chapurlat RD, Christiansen C, Cummings SR, Diez-Perez A, Eisman JA, Fujiwara S, Gluer CC, Goltzman D, Hans D, Khaw KT, Krieg MA, Kroger H, LaCroix AZ, Lau E, Leslie WD, Mellstrom D, Melton LJ 3rd, O'Neill TW, Pasco JA, Prior JC, Reid DM, Rivadeneira F, van Staa T, Yoshimura N, Zillikens MC. A meta-analysis of the association of fracture risk and body mass index in women. J Bone Miner Res. 2014 Jan;29(1):223-33. doi: 10.1002/jbmr.2017.

  PMID: 23775829 BACKGROUND

• Kim JH, Choi HJ, Ku EJ, Kim KM, Kim SW, Cho NH, Shin CS. Trabecular bone score as an indicator for skeletal deterioration in diabetes. J Clin Endocrinol Metab. 2015 Feb;100(2):475-82. doi: 10.1210/jc.2014-2047. Epub 2014 Nov 4.

  PMID: 25368976 BACKGROUND

• Leslie WD, Aubry-Rozier B, Lamy O, Hans D; Manitoba Bone Density Program. TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab. 2013 Feb;98(2):602-9. doi: 10.1210/jc.2012-3118. Epub 2013 Jan 22.

  PMID: 23341489 BACKGROUND

• Leslie WD, Rubin MR, Schwartz AV, Kanis JA. Type 2 diabetes and bone. J Bone Miner Res. 2012 Nov;27(11):2231-7. doi: 10.1002/jbmr.1759. Epub 2012 Sep 28.

  PMID: 23023946 BACKGROUND

• Martyn-St James M, Carroll S. Effects of different impact exercise modalities on bone mineral density in premenopausal women: a meta-analysis. J Bone Miner Metab. 2010 May;28(3):251-67. doi: 10.1007/s00774-009-0139-6. Epub 2009 Dec 15.

  PMID: 20013013 BACKGROUND

• Napoli N, Strotmeyer ES, Ensrud KE, Sellmeyer DE, Bauer DC, Hoffman AR, Dam TT, Barrett-Connor E, Palermo L, Orwoll ES, Cummings SR, Black DM, Schwartz AV. Fracture risk in diabetic elderly men: the MrOS study. Diabetologia. 2014 Oct;57(10):2057-65. doi: 10.1007/s00125-014-3289-6. Epub 2014 Jun 9.

  PMID: 24908567 BACKGROUND

• Park SW, Goodpaster BH, Strotmeyer ES, de Rekeneire N, Harris TB, Schwartz AV, Tylavsky FA, Newman AB. Decreased muscle strength and quality in older adults with type 2 diabetes: the health, aging, and body composition study. Diabetes. 2006 Jun;55(6):1813-8. doi: 10.2337/db05-1183.

  PMID: 16731847 BACKGROUND

• Petit MA, Paudel ML, Taylor BC, Hughes JM, Strotmeyer ES, Schwartz AV, Cauley JA, Zmuda JM, Hoffman AR, Ensrud KE; Osteoporotic Fractures in Men (MrOs) Study Group. Bone mass and strength in older men with type 2 diabetes: the Osteoporotic Fractures in Men Study. J Bone Miner Res. 2010 Feb;25(2):285-91. doi: 10.1359/jbmr.090725.

  PMID: 19594301 BACKGROUND

• Schwartz AV, Hillier TA, Sellmeyer DE, Resnick HE, Gregg E, Ensrud KE, Schreiner PJ, Margolis KL, Cauley JA, Nevitt MC, Black DM, Cummings SR. Older women with diabetes have a higher risk of falls: a prospective study. Diabetes Care. 2002 Oct;25(10):1749-54. doi: 10.2337/diacare.25.10.1749.

  PMID: 12351472 BACKGROUND

• Schwartz AV, Sellmeyer DE, Ensrud KE, Cauley JA, Tabor HK, Schreiner PJ, Jamal SA, Black DM, Cummings SR; Study of Osteoporotic Features Research Group. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab. 2001 Jan;86(1):32-8. doi: 10.1210/jcem.86.1.7139.

  PMID: 11231974 BACKGROUND

• Tao B, Liu JM, Zhao HY, Sun LH, Wang WQ, Li XY, Ning G. Differences between measurements of bone mineral densities by quantitative ultrasound and dual-energy X-ray absorptiometry in type 2 diabetic postmenopausal women. J Clin Endocrinol Metab. 2008 May;93(5):1670-5. doi: 10.1210/jc.2007-1760. Epub 2008 Mar 4.

  PMID: 18319321 BACKGROUND

• Vestergaard P. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int. 2007 Apr;18(4):427-44. doi: 10.1007/s00198-006-0253-4. Epub 2006 Oct 27.

  PMID: 17068657 BACKGROUND

• Balducci S, Conti F, Sacchetti M, Russo CR, Argento G, Haxhi J, Orlando G, Rapisarda G, D'Errico V, Cardelli P, Pugliese L, Laghi A, Vitale M, Bollanti L, Zanuso S, Nicolucci A, Pugliese G; SWEET BONE Investigators. Study to Weigh the Effect of Exercise Training on BONE quality and strength (SWEET BONE) in type 2 diabetes: study protocol for a randomised clinical trial. BMJ Open. 2019 Nov 4;9(11):e027429. doi: 10.1136/bmjopen-2018-027429.

  PMID: 31690602 DERIVED

Related Links

• Web site of the Metabolic Fitness Association

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Fractures, Bone

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Wounds and Injuries

Study Officials

• Giuseppe Pugliese, MD, PhD

  University of Roma La Sapienza

  PRINCIPAL INVESTIGATOR

• Francesco Conti, MD, PhD

  University of Roma La Sapienza

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: April 20, 2015
• Study Start: October 1, 2018
• Primary Completion: November 1, 2023
• Study Completion: March 1, 2024
• Last Updated: March 22, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)