Exploring Time-efficient Strategies to Improve Fitness for Surgery in Older Adults

Hypertension Clinical Trial

— eHHH  

Official title:

Exploring Time-efficient Strategies to Improve Fitness for Surgery in Older Adults

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03019146
• Other study ID #: A12092016
• Status: Active, not recruiting
• Phase: N/A
• Start date: January 4, 2017
• Est. completion date: August 1, 2019

Study information

• Verified date: May 2019
• Source: University of Nottingham
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The incidence of conditions requiring surgical intervention increases with age, however there is a reported decline in the rates of elective surgical procedures in those over 65. This is associated with older patients being described as "less fit" and more at risk of postoperative complications, leading to decreased provision of surgical care to those at need. Exercise interventions have the potential to reverse some of the decline in cardiovascular fitness associated with aging and improve the elderly's' "fitness for surgery" and potentially allow increased access to surgical care for those most in need of it.

Description:

The percentage of people aged >65 y in the United Kingdom increased from 15% in 1985 to 17% in 2010, an increase of 1.7 million people. One age-associated physiological change is the reduction in vascular function that is observed, both at the levels of the large arteries and the muscle microvasculature. In itself this vascular dysfunction is associated with reduced aerobic performance. Cardiorespiratory fitness (marked by aerobic performance) has been shown to be an independent predictor of postoperative mortality, which provides more accurate prognostic information than age alone. In contrast, physical activity can reverse elements of pathophysiology associated with these conditions, including vascular dysfunction. Nonetheless, major roadblocks to exercise as a strategy to combat age-associated vascular dysfunction and associated conditions exist, namely: i) poor exercise tolerance, ii) "lack of time", iii) age-related mobility impairments, and iv) exercise resistance.

The aim of this study is to investigate whether if novel low-volume, time-efficient training strategies can improve indices of vascular health and cardiorespiratory performance in older individuals with a view towards improving their fitness for surgery. Numerous studies have demonstrated that periods of supervised exercise training effectively improve indices of cardiorespiratory (blood pressure, aerobic capacity and blood lipids and vascular function. However, the majority of these studies were conducted using high-volume continuous submaximal aerobic training (e.g. 50-65% VO2max for 30-60 min) or moderate to high volume progressive weight training. This research group have recently shown the efficacy of a time-efficient exercise strategy known as HIIT - High Intensity Interval Training, for improving VO2 max and muscle mass in young individuals with heightened metabolic disease risk and also demonstrated significant improvements in VO2 max comparable to classic aerobic exercise training using several different time-efficient HIIT protocols. However, despite the potential benefits of HIIT, not least its 70-80% reduction in required time-commitment compared to current WHO guidelines, it does have limitations, particularly for an older population where physical (mobility/joint) and/or socio-economic (transport/gym access/equipment purchase) barriers may render it ineffective and/or unachievable.

Alternative interventions for prevention or treatment of age-associated vascular dysfunction could be provided by isometric handgrip training (IHG) or remote ischaemic pre-conditioning (RIPC), both of which have a similar low time-commitment compared to HIIT but are less strenuous, have potential as home-based interventions, and require only inexpensive equipment. IHG has been demonstrated to improve resting blood pressure in both normotensive and medicated hypertensive populations to a similar or greater extent as classic aerobic exercise training. However, the effects of IHG on other vascular (e.g. limb, brain and muscle microvascular blood flow) or cardio-respiratory parameters (VO2 max, heart rate (resting/recovery), exercise tolerance) have not been assessed. Similarly, although RIPC has recently been shown to improve maximal athletic cardio-respiratory performance and vascular function in young subjects, no work to date has explored the efficacy of chronic RIPC on indices of health or vascular function in older individuals.

Therefore, the aims of this project are to:

(i) Assess the efficacy of 6 weeks HIT, IHG and RIPC for improving indices of cardio-respiratory, vascular and metabolic function in older subjects as a means of improving fitness for surgery.

(ii) Explore the concept of "exercise resistance" in relation to HIT, IHG and RIPC by:

1. Assessing if the same degree of response heterogeneity exists for the three time-efficient training modes employed in this study as has been reported for classic resistance and aerobic exercise training

2. Assessing if a "non-responder" for one index (i.e., resting blood pressure or leg blood flow) is a non-responder for all other indices

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: August 1, 2019
• Est. primary completion date: April 25, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

• Healthy volunteer aged 65-85

Exclusion Criteria:

• • Current participation in a formal exercise regime

• A BMI < 18 or > 32 kg·m2

• Active cardiovascular disease:

• uncontrolled hypertension (BP > 160/100),

• angina,

• heart failure (class III/IV),

• Significant arrhythmia,

• right to left cardiac shunt,

• recent cardiac event

• Taking beta-adrenergic blocking agents,

• Cerebrovascular disease:

• previous stroke,

• aneurysm (large vessel or intracranial)

• epilepsy

• Respiratory disease including:

• pulmonary hypertension,

• Significant COPD,

• Uncontrolled asthma,

• Metabolic disease:

• hyper and hypo parathyroidism,

• untreated hyper and hypothyroidism,

• Cushing's disease,

• type 1 or 2 diabetes

• Active inflammatory bowel or renal disease

• Malignancy

• Clotting dysfunction

• Significant Musculoskeletal or neurological disorders

• Family history of early (<55y) death from cardiovascular disease

• Known sensitivity to Sonovue

Related Conditions & MeSH terms

• Hypertension
• Perioperative Hypertension

Intervention

Other:
• HIIT

• HOLD

• HUG

Locations

Country	Name	City	State
United Kingdom	University Of Nottingham	Derby

Sponsors (3)

Lead Sponsor	Collaborator
University of Nottingham	The Dunhill Medical Trust, The Royal College of Surgeons of England

Country where clinical trial is conducted

United Kingdom, 

References & Publications (18)

Church TS, Earnest CP, Skinner JS, Blair SN. Effects of different doses of physical activity on cardiorespiratory fitness among sedentary, overweight or obese postmenopausal women with elevated blood pressure: a randomized controlled trial. JAMA. 2007 May 16;297(19):2081-91. — View Citation

Garg R, Malhotra V, Kumar A, Dhar U, Tripathi Y. Effect of isometric handgrip exercise training on resting blood pressure in normal healthy adults. J Clin Diagn Res. 2014 Sep;8(9):BC08-10. doi: 10.7860/JCDR/2014/8908.4850. Epub 2014 Sep 20. — View Citation

González-Alonso J, Calbet JA. Reductions in systemic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans. Circulation. 2003 Feb 18;107(6):824-30. — View Citation

Iwasaki K, Zhang R, Zuckerman JH, Levine BD. Dose-response relationship of the cardiovascular adaptation to endurance training in healthy adults: how much training for what benefit? J Appl Physiol (1985). 2003 Oct;95(4):1575-83. Epub 2003 Jun 27. — View Citation

Jean-St-Michel E, Manlhiot C, Li J, Tropak M, Michelsen MM, Schmidt MR, McCrindle BW, Wells GD, Redington AN. Remote preconditioning improves maximal performance in highly trained athletes. Med Sci Sports Exerc. 2011 Jul;43(7):1280-6. doi: 10.1249/MSS.0b013e318206845d. — View Citation

Jones H, Hopkins N, Bailey TG, Green DJ, Cable NT, Thijssen DH. Seven-day remote ischemic preconditioning improves local and systemic endothelial function and microcirculation in healthy humans. Am J Hypertens. 2014 Jul;27(7):918-25. doi: 10.1093/ajh/hpu004. Epub 2014 Mar 13. — View Citation

Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, Bales CW, Henes S, Samsa GP, Otvos JD, Kulkarni KR, Slentz CA. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002 Nov 7;347(19):1483-92. — View Citation

Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP, Houmard JA, Slentz CA. Studies of a targeted risk reduction intervention through defined exercise (STRRIDE). Med Sci Sports Exerc. 2001 Oct;33(10):1774-84. — View Citation

LaRocca TJ, Hearon CM Jr, Henson GD, Seals DR. Mitochondrial quality control and age-associated arterial stiffening. Exp Gerontol. 2014 Oct;58:78-82. doi: 10.1016/j.exger.2014.07.008. Epub 2014 Jul 14. — View Citation

Metcalfe RS, Babraj JA, Fawkner SG, Vollaard NB. Towards the minimal amount of exercise for improving metabolic health: beneficial effects of reduced-exertion high-intensity interval training. Eur J Appl Physiol. 2012 Jul;112(7):2767-75. doi: 10.1007/s00421-011-2254-z. Epub 2011 Nov 29. — View Citation

Millar PJ, McGowan CL, Cornelissen VA, Araujo CG, Swaine IL. Evidence for the role of isometric exercise training in reducing blood pressure: potential mechanisms and future directions. Sports Med. 2014 Mar;44(3):345-56. doi: 10.1007/s40279-013-0118-x. Review. — View Citation

Phillips B, Williams J, Atherton P, Smith K, Hildebrandt W, Rankin D, Greenhaff P, Macdonald I, Rennie MJ. Resistance exercise training improves age-related declines in leg vascular conductance and rejuvenates acute leg blood flow responses to feeding and exercise. J Appl Physiol (1985). 2012 Feb;112(3):347-53. doi: 10.1152/japplphysiol.01031.2011. Epub 2011 Oct 13. — View Citation

Phillips BE, Atherton PJ, Varadhan K, Limb MC, Wilkinson DJ, Sjøberg KA, Smith K, Williams JP. The effects of resistance exercise training on macro- and micro-circulatory responses to feeding and skeletal muscle protein anabolism in older men. J Physiol. 2015 Jun 15;593(12):2721-34. doi: 10.1113/JP270343. Epub 2015 May 14. — View Citation

Santos-Parker JR, LaRocca TJ, Seals DR. Aerobic exercise and other healthy lifestyle factors that influence vascular aging. Adv Physiol Educ. 2014 Dec;38(4):296-307. doi: 10.1152/advan.00088.2014. Review. — View Citation

Seals DR. Edward F. Adolph Distinguished Lecture: The remarkable anti-aging effects of aerobic exercise on systemic arteries. J Appl Physiol (1985). 2014 Sep 1;117(5):425-39. doi: 10.1152/japplphysiol.00362.2014. Epub 2014 May 22. Review. — View Citation

Snowden CP, Prentis J, Jacques B, Anderson H, Manas D, Jones D, Trenell M. Cardiorespiratory fitness predicts mortality and hospital length of stay after major elective surgery in older people. Ann Surg. 2013 Jun;257(6):999-1004. doi: 10.1097/SLA.0b013e31828dbac2. — View Citation

Vollaard NB, Constantin-Teodosiu D, Fredriksson K, Rooyackers O, Jansson E, Greenhaff PL, Timmons JA, Sundberg CJ. Systematic analysis of adaptations in aerobic capacity and submaximal energy metabolism provides a unique insight into determinants of human aerobic performance. J Appl Physiol (1985). 2009 May;106(5):1479-86. doi: 10.1152/japplphysiol.91453.2008. Epub 2009 Feb 5. — View Citation

Wilmore JH, Green JS, Stanforth PR, Gagnon J, Rankinen T, Leon AS, Rao DC, Skinner JS, Bouchard C. Relationship of changes in maximal and submaximal aerobic fitness to changes in cardiovascular disease and non-insulin-dependent diabetes mellitus risk factors with endurance training: the HERITAGE Family Study. Metabolism. 2001 Nov;50(11):1255-63. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in resting systolic blood pressure	Measured in seated position using oscillometry, mean value of 3 recordings, measured according to British Society of Hypertension Guidelines 2013.	6 weeks
Secondary	Change in resting diastolic blood pressure	Measured using a ramp incremental exercise test on a cycle ergometer.	6 weeks
Secondary	Ambulatory blood pressure	Ambulatory blood pressure	6 weeks
Secondary	V02 Peak	Measured using a ramp incremental exercise test on a cycle ergometer.	6 weeks
Secondary	Anaerobic threshold	Measured using a ramp incremental exercise test on a cycle ergometer.	6 weeks
Secondary	Body fat percentage	Measured by dual energy X-ray absorptiometry	6 weeks
Secondary	Total body lean mass	Measured by dual energy X-ray absorptiometry	6 weeks
Secondary	Change in common femoral artery blood flow	Measured by duplex ultrasound on non-dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum	6 weeks
Secondary	Change in Vastus lateralis microvascular blood flow	Measured by contrast enhanced ultrasound on the dominant leg in response to 6 unilateral leg extensions at 50% 1 repetition maximum	6 weeks
Secondary	Flow-mediated dilatation		6 weeks
Secondary	Heart rate recovery post exercise	Change in heart rate after exercise from peak over time	6 weeks
Secondary	Blood pressure recovery post exercise	Change in blood pressure after exercise from peak over time	6 weeks
Secondary	Area under concentration curve for serum Glucose	Measured from a 3 hour oral glucose tolerance test	6 weeks
Secondary	Area under concentration curve for serum Insulin	Measured from a 3 hour oral glucose tolerance test	6 weeks
Secondary	Matsuda Index of insulin sensitivity	Measured from a 3 hour oral glucose tolerance test	6 weeks
Secondary	Cederholm Index of insulin sensitivity	Measured from a 3 hour oral glucose tolerance test	6 weeks
Secondary	Homeostatic Model Assessment of Insulin Resistance	Measured from fasting plasma samples, taken before a 3 hour oral glucose tolerance test	6 weeks
Secondary	Fasting Serum Cholesterol		6 weeks
Secondary	Fasting serum triglyceride		6 weeks
Secondary	Time to failure, cycling at 50% maximum power achieved during CPET		6 weeks
Secondary	Handgrip maximum voluntary contraction	Measured using a handgrip dynamometer	6 weeks

External Links

•   Office for National Statistics; Population Ageing in the United Kingdom, its Constituent Countries and the European Union