Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Trials
Published in: Trials 1/2014

Open Access 01-12-2014 | Study protocol

Pre-Operative nutrition In Neck of femur Trial (POINT) - carbohydrate loading in patients with fragility hip fracture: study protocol for a randomised controlled trial

Authors: Iain K Moppett, Paul L Greenhaff, Ben J Ollivere, Theophillus Joachim, Dileep N Lobo, Martin Rowlands

Published in: Trials | Issue 1/2014

Login to get access

Abstract

Background

Trauma such as hip fracture initiates a neurohumoral stress response that changes the balance between anabolism and catabolism resulting in muscle breakdown and reduced mobilisation. Various studies have demonstrated a reduction in catabolism with pre-operative carbohydrate loading but only in an elective setting.

Methods/Design

This is a two-centre, randomised double-blinded trial in the United Kingdom. Sample size will be 30 patients (approximately 15 from each centre).
Randomisation will be web based using computer-generated concealed tables. Both participants and investigators will be blinded to group allocation.
Participants will be >70 years of age, cognitively intact (Abbreviated Mental Score ≥7), able to give informed consent, and admitted directly through the emergency department with fractured neck of femur requiring hemiarthroplasty.
Intervention will consist of two carbohydrate drinks (Nutricia pre-Op) given the night before, and the morning of the surgery. The control will receive two placebo drinks of equal volume.
All participants will receive standard hospital care at the discretion of the clinical team. The primary outcome is the difference between groups in insulin resistance calculated by a glucose tolerance test administered pre-operatively and 24 hours postoperatively. Secondary endpoints will be changes in muscle carbohydrate metabolism (biopsy), mobility (Cumulative Ambulation Score) and subjective measures of tolerability.

Discussion

This is a small-scale pilot study, investigating the benefits and tolerability of carbohydrate loading in an emergency setting in a frail elderly group with known high morbidity and mortality. Positive findings will provide the basis for a larger scale study.

Trial registration

Current Controlled Trials ISRCTN91109766 (7 April 2014); NRES ref: 13/EM/0214
Trial Sponsor: University of Nottingham Ref.13036.
Literature
1.
Thorell ANJ, Ljungqvist O: Insulin resistance: a marker of surgical stress. Curr Opin Clin Nutr Metab Care. 1999, 2: 69-78. 10.1097/00075197-199901000-00012.CrossRefPubMed
2.
Beck Nielsen H: General characteristics of the insulin resistance syndrome: prevalence and heritability. European group for the study of insulin resistance (EGIR). Drugs. 1999, 58 (Suppl 1): 7-10.CrossRefPubMed
3.
Ljungqvist O: Insulin resistance and outcomes in surgery. J Clin Endocrinol Metab. 2010, 95: 4217-4219. 10.1210/jc.2010-1525.CrossRefPubMed
4.
Nygren J, Thorell A, Brismar K, Karpe F, Ljungqvist O: Short-term hypocaloric nutrition but not bed rest decrease insulin sensitivity and IGF-I bioavailability in healthy subjects: the importance of glucagon. Nutrition. 1997, 13: 945-951. 10.1016/S0899-9007(97)00335-3.CrossRefPubMed
5.
Sato H, Carvalho G, Sato T, Lattermann R, Matsukawa T, Schricker T: The association of preoperative glycemic control, intraoperative insulin sensitivity, and outcomes after cardiac surgery. J Clin Endocrinol Metab. 2010, 95: 4338-4344. 10.1210/jc.2010-0135.CrossRefPubMed
6.
Hedström M, Sääf M, Dalén N: Low IGF-I levels in hip fracture patients. A comparison of 20 coxarthrotic and 23 hip fracture patients. Acta Orthop Scand. 1999, 70: 145-148. 10.3109/17453679909011253.CrossRefPubMed
7.
Ljungqvist O, Soop M, Hedstrom M: Why metabolism matters in elective orthopedic surgery: a review. Acta Orthop. 2007, 78: 610-615. 10.1080/17453670710014293.CrossRefPubMed
8.
Veenhof AAFA, Sietses C, Von Blomberg BME, Van Hoogstraten IMW, VD Pas MHGM, Meijerink WJHJ, VD Peet DL, VD Tol MP, Bonjer HJ, Cuesta MA: The surgical stress response and postoperative immune function after laparoscopic or conventional total mesorectal excision in rectal cancer: a randomized trial. Int J Color Dis. 2011, 26: 53-59. 10.1007/s00384-010-1056-9.CrossRef
9.
Ahlers O, Nachtigall I, Lenze J, Goldmann A, Schulte E, Hohne C, Fritz G, Keh D: Intraoperative thoracic epidural anaesthesia attenuates stress-induced immunosuppression in patients undergoing major abdominal surgery. Br J Anaesth. 2008, 101: 781-787. 10.1093/bja/aen287.CrossRefPubMed
10.
White SM, Griffiths R, Moppett IK: Type of anaesthesia for hip fracture surgery - the problems of trial design. Anaesthesia. 2012, 67: 571-574. 10.1111/j.1365-2044.2012.07166.x.CrossRef
11.
Varadhan KK, Neal KR, Dejong CH, Fearon KC, Ljungqvist O, Lobo DN: The enhanced recovery after surgery (ERAS) pathway for patients undergoing major elective open colorectal surgery: a meta-analysis of randomized controlled trials. Clin Nutr. 2010, 29: 434-440. 10.1016/j.clnu.2010.01.004.CrossRefPubMed
12.
Soop M, Nygren J, Myrenfors P, Thorell A, Ljungqvist O: Preoperative oral carbohydrate treatment attenuates immediate postoperative insulin resistance. Am J Physiol Endocrinol Metab. 2001, 280: E576-E583.PubMed
13.
Hausel J, Nygren J, Thorell A, Lagerkranser M, Ljungqvist O: Randomized clinical trial of the effects of oral preoperative carbohydrates on postoperative nausea and vomiting after laparoscopic cholecystectomy. Br J Surg. 2005, 92: 415-421. 10.1002/bjs.4901.CrossRefPubMed
14.
Hausel J, Nygren J, Lagerkranser M, Hellstrom PM, Hammarqvist F, Almstrom C, Lindh A, Thorell A, Ljungqvist O: A carbohydrate-rich drink reduces preoperative discomfort in elective surgery patients. Anesth Analg. 2001, 93: 1344-1350. 10.1097/00000539-200111000-00063.CrossRefPubMed
15.
Yuill KA, Richardson RA, Davidson HI, Garden OJ, Parks RW: The administration of an oral carbohydrate-containing fluid prior to major elective upper-gastrointestinal surgery preserves skeletal muscle mass postoperatively–a randomised clinical trial. Clin Nutr. 2005, 24: 32-37. 10.1016/j.clnu.2004.06.009.CrossRefPubMed
16.
Ljungqvist O, Nygren J, Thorell A: Modulation of post-operative insulin resistance by pre-operative carbohydrate loading. Proc Nutrition Society. 2002, 61: 329-336. 10.1079/PNS2002168.CrossRef
17.
Lobo DN, Hendry PO, Rodrigues G, Marciani L, Totman JJ, Wright JW, Preston T, Gowland P, Spiller RC, Fearon KC: Gastric emptying of three liquid oral preoperative metabolic preconditioning regimens measured by magnetic resonance imaging in healthy adult volunteers: a randomised double-blind, crossover study. Clin Nutr. 2009, 28: 636-641. 10.1016/j.clnu.2009.05.002.CrossRefPubMed
18.
Yagci G, Can MF, Ozturk E, Dag B, Ozgurtas T, Cosar A, Tufan T: Effects of preoperative carbohydrate loading on glucose metabolism and gastric contents in patients undergoing moderate surgery: a randomized, controlled trial. Nutrition. 2008, 24: 212-216. 10.1016/j.nut.2007.11.003.CrossRefPubMed
19.
Ljungqvist O, Boija PO, Esahili H, Larsson M, Ware J: Food deprivation alters liver glycogen metabolism and endocrine responses to hemorrhage. Am J Physiol. 1990, 259: E692-E698.PubMed
20.
Awad S, Constantin-Teodosiu D, Macdonald IA, Lobo DN: Short-term starvation and mitochondrial dysfunction - a possible mechanism leading to postoperative insulin resistance. Clin Nutr. 2009, 28: 497-509. 10.1016/j.clnu.2009.04.014.CrossRefPubMed
21.
Witasp A, Nordfors L, Schalling M, Nygren J, Ljungqvist O, Thorell A: Increased expression of inflammatory pathway genes in skeletal muscle during surgery. Clin Nutr. 2009, 28: 291-298. 10.1016/j.clnu.2009.03.003.CrossRefPubMed
22.
Witasp A, Nordfors L, Schalling M, Nygren J, Ljungqvist O, Thorell A: Expression of inflammatory and insulin signaling genes in adipose tissue in response to elective surgery. J Clin Endocrinol Metab. 2010, 95: 3460-3469. 10.1210/jc.2009-2588.CrossRefPubMed
23.
Crossland H, Constantin-Teodosiu D, Gardiner SM, Constantin D, Greenhaff PL: A potential role for Akt/FOXO signalling in both protein loss and the impairment of muscle carbohydrate oxidation during sepsis in rodent skeletal muscle. J Physiol. 2008, 586: 5589-5600. 10.1113/jphysiol.2008.160150.CrossRefPubMedPubMedCentral
24.
Constantin D, McCullough J, Mahajan RP, Greenhaff PL: Novel events in the molecular regulation of muscle mass in critically ill patients. J Physiol. 2011, 589: 3883-3895. 10.1113/jphysiol.2011.206193.CrossRefPubMedPubMedCentral
25.
Awad S, Constantin-Teodosiu D, Constantin D, Rowlands BJ, Fearon KC, Macdonald IA, Lobo DN: Cellular mechanisms underlying the protective effects of preoperative feeding: a randomized study investigating muscle and liver glycogen content, mitochondrial function, gene and protein expression. Ann Surg. 2010, 252: 247-253. 10.1097/SLA.0b013e3181e8fbe6.CrossRefPubMed
26.
Varadhan KK, Atkins RP, Constantin-Teodosiu D, Elaine B, Perkins AC, Greenhaff PL, Lobo DN: Gastrointestinal surgery mediated increases in gut permeability and expression of IL6 and PDK4 mRNAs in quadriceps muscle may underpin the post-operative increase in whole-body insulin resistance in humans. J Am Coll Surg. 2011, 213: S53-10.1016/j.jamcollsurg.2011.06.114.CrossRef
27.
Atkins RP, Varadhan KK, Constantin-Teodosiu D, Lobo DN, Greenhaff PL: Rates of skeletal muscle mitochondrial ATP production are reduced during elective abdominal surgery in humans. J Am Coll Surg. 2011, 213: S59-CrossRef
28.
Murton AJ, Constantin D, Greenhaff PL: The involvement of the ubiquitin proteasome system in human skeletal muscle remodelling and atrophy. Biochim Biophys Acta. 2008, 1782: 730-743. 10.1016/j.bbadis.2008.10.011.CrossRefPubMed
29.
Kim YI, Lee FN, Choi WS, Lee S, Youn JH: Insulin regulation of skeletal muscle PDK4 mRNA expression is impaired in acute insulin-resistant states. Diabetes. 2006, 55: 2311-2317. 10.2337/db05-1606.CrossRefPubMed
30.
Koopman R, Van Loon LJ: Aging, exercise, and muscle protein metabolism. J Appl Physiol (1985). 2009, 106: 2040-2048. 10.1152/japplphysiol.91551.2008.CrossRef
31.
White SM, Griffiths R: Projected incidence of proximal femoral fracture in England: a report from the NHS Hip Fracture Anaesthesia Network (HIPFAN). Injury. 2011, 42: 1230-1233. 10.1016/j.injury.2010.11.010.CrossRefPubMed
32.
Maxwell MJ, Moran CG, Moppett IK: Development and validation of a preoperative scoring system to predict 30 day mortality in patients undergoing hip fracture surgery. Br J Anaesth. 2008, 101: 511-517. 10.1093/bja/aen236.CrossRefPubMed
33.
Wiles MD, Moran CG, Sahota O, Moppett IK: Nottingham Hip fracture score as a predictor of one year mortality in patients undergoing surgical repair of fractured neck of femur. Br J Anaesth. 2011, 106: 501-504. 10.1093/bja/aeq405.CrossRefPubMed
34.
Foss NB, Kristensen MT, Kehlet H: Prediction of postoperative morbidity, mortality and rehabilitation in hip fracture patients: the cumulated ambulation score. Clin Rehabil. 2006, 20: 701-708. 10.1191/0269215506cre987oa.CrossRefPubMed
35.
Fox KM, Hawkes WG, Hebel JR, Felsenthal G, Clark M, Zimmerman SI, Kenzora JE, Magaziner J: Mobility after hip fracture predicts health outcomes. J Am Geriatr Soc. 1998, 46: 169-173.CrossRefPubMed
36.
Beloosesky Y, Weiss A, Manasian M, Salai M: Handgrip strength of the elderly after hip fracture repair correlates with functional outcome. Disabil Rehabil. 2010, 32: 367-373. 10.3109/09638280903168499.CrossRefPubMed
37.
Pedersen SJ, Borgbjerg FM, Schousboe B, Pedersen BD, Jorgensen HL, Duus BR, Lauritzen JB: A comprehensive hip fracture program reduces complication rates and mortality. J Am Geriatr Soc. 2008, 56: 1831-1838. 10.1111/j.1532-5415.2008.01945.x.CrossRefPubMed
38.
Gunnarsson AK, Lonn K, Gunningberg L: Does nutritional intervention for patients with hip fractures reduce postoperative complications and improve rehabilitation?. J Clin Nurs. 2009, 18: 1325-1333. 10.1111/j.1365-2702.2008.02673.x.CrossRefPubMed
39.
Kudoh A, Ishihara H, Matsuki A: Response to surgical stress in elderly patients and Alzheimer’s disease. Can J Anesth. 1999, 46: 247-252. 10.1007/BF03012604.CrossRefPubMed
40.
Kudoh A, Katagai H, Takazawa T, Matsuki A: Plasma proinflammatory cytokine response to surgical stress in elderly patients. Cytokine. 2001, 15: 270-273. 10.1006/cyto.2001.0927.CrossRefPubMed
41.
Sun T, Wang X, Liu Z, Chen X, Zhang J: Plasma concentrations of pro- and anti-inflammatory cytokines and outcome prediction in elderly hip fracture patients. Injury. 2011, 42: 707-713. 10.1016/j.injury.2011.01.010.CrossRefPubMed
42.
Mathur S, Plank L, McCall J, Shapkov P, McIlroy K, Gillanders L, Merrie A, Torrie J, Pugh F, Koea J: Randomized controlled trial of preoperative oral carbohydrate treatment in major abdominal surgery. Br J Surg. 2010, 97: 485-494. 10.1002/bjs.7026.CrossRefPubMed
43.
Perrone F, Da Silva Filho AC, Adorno IF, Anabuki NT, Leal FS, Colombo TDA, Silva BD, Dock Nascimento DB, Damiao A, De Aguilar-Nascimento JE: Effects of preoperative feeding with a whey protein plus carbohydrate drink on the acute phase response and insulin resistance. A randomized trial. Nutr J. 2011, 10: 66-10.1186/1475-2891-10-66.CrossRefPubMedPubMedCentral
44.
Blichert-Toft M, Christensen V, Engquist A, Fog-Moller F, Kehlet H, Madsen SN, Skovsted L, Thode J, Olgaard K: Influence of age on the endocrine-metabolic response to surgery. Ann Surg. 1979, 190: 761-770. 10.1097/00000658-197912000-00017.CrossRefPubMedPubMedCentral
45.
Oyama T, Taniguchi K, Takazawa T, Matsuki A, Kudo M: Effect of anaesthesia and surgery on endocrine function in elderly patients. Can Anaesth Soc J. 1980, 27: 556-559. 10.1007/BF03006885.CrossRefPubMed
46.
Fox KMMJ, Hawkes WG, Yu Yahiro J, Hebel JR, Zimmerman SI, Holder L, Michael R: Loss of bone density and lean body mass after hip fracture. Osteoporos Int. 2000, 11: 31-35. 10.1007/s001980050003.CrossRefPubMed
47.
Adunsky A, Chandler J, Heyden N, Lutkiewicz J, Scott BB, Berd Y, Liu N, Papanicolaou DA: MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study. Arch Gerontol Geriatr. 2011, 53: 183-189. 10.1016/j.archger.2010.10.004.CrossRefPubMed
48.
Yeo AL, Levy D, Martin FC, Sonksen P, Sturgess I, Wheeler MM, Young A: Frailty and the biochemical effects of recombinant human growth hormone in women after surgery for hip fracture. Growth Hormon IGF Res. 2003, 13: 361-370. 10.1016/j.ghir.2003.08.001.CrossRef
49.
Lawson RM, Doshi MK, Barton JR, Cobden I: The effect of unselected post-operative nutritional supplementation on nutritional status and clinical outcome of orthopaedic patients. Clin Nutr. 2003, 22: 39-46. 10.1054/clnu.2002.0588.CrossRefPubMed
50.
Avenell A, Handoll HH: Nutritional supplementation for hip fracture aftercare in older people. Cochrane Database Syst Rev. 2010, 1: CD001880-PubMed
51.
52.
53.
Wiles MD, Whiteley WJ, Moran CG, Moppett IK: The use of LiDCO based fluid management in patients undergoing hip fracture surgery under spinal anaesthesia: neck of femur optimisation therapy - targeted stroke volume (NOTTS): study protocol for a randomized controlled trial. Trials. 2011, 12: 213-10.1186/1745-6215-12-213.CrossRefPubMedPubMedCentral
54.
55.
International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH): Guidance for Industry E6 Good Clinical Practice. 1996, Rockville, MD: Consolidated Guidance
56.
57.
Department of Health Payment by Results Team: Payment by Results Guidance for 2013–14. 2013, London: Department of Health
Metadata
Title
Pre-Operative nutrition In Neck of femur Trial (POINT) - carbohydrate loading in patients with fragility hip fracture: study protocol for a randomised controlled trial
Authors
Iain K Moppett
Paul L Greenhaff
Ben J Ollivere
Theophillus Joachim
Dileep N Lobo
Martin Rowlands
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Trials / Issue 1/2014
Electronic ISSN: 1745-6215
DOI
https://doi.org/10.1186/1745-6215-15-475

Other articles of this Issue 1/2014

Trials 1/2014 Go to the issue

Study protocol

Efficacy of two different self-expanding nitinol stents for atherosclerotic femoropopliteal arterial disease (SENS-FP trial): study protocol for a randomized controlled trial

Study protocol

The ENHANCES study—Enhancing Head and Neck Cancer patients’ Experiences of Survivorship: study protocol for a randomized controlled trial

Study protocol

FAIRY: a randomized controlled patient-blind phase III study to compare the efficacy and safety of intravenous ferric carboxymaltose (Ferinject®) to placebo in patients with acute isovolemic anemia after gastrectomy - study protocol for a randomized controlled trial

Editorial

Linked publications from a single trial: a thread of evidence

Study protocol

The effect of changing stool collection processes on compliance in nationwide organized screening using a fecal occult blood test (FOBT) in Korea: study protocol for a randomized controlled trial

Study protocol

A multi-site single-blind clinical study to compare the effects of STAIR Narrative Therapy to treatment as usual among women with PTSD in public sector mental health settings: study protocol for a randomized controlled trial