Effect of exercise training and dopamine agonists in patients with uremic restless legs syndrome: a six-month randomized, partially double-blind, placebo-controlled comparative study

BMC Nephrology

Ioannis Stefanidis²  Yiannis Koutedakis³  Theodoros Kyriakides⁶  Eleftherios Lavdas⁴  Georgios M Hadjigeorgiou⁵  Christina Karatzaferi³  Giorgos K Sakkas³  Christoforos D Giannaki¹ 

[1] Department of Life & Health Sciences, University of Nicosia, Nicosia, Cyprus;Department of Nephrology, School of Medicine, University of Thessaly, Larissa, Greece;Institute for Research and Technology Thessaly, Center for Research and Technology Hellas, Trikala, Greece;Department of Radiology, School of Medicine, University of Thessaly, Larissa, Greece;Department of Neurology, School of Medicine, University of Thessaly, Larissa, Greece;The Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus

关键词: Sleep;    Quality of life;    Muscle atrophy;    Lean body mass;    Extramyocellular lipids;   

Others  :  1082845
DOI  :  10.1186/1471-2369-14-194

 received in 2012-07-09, accepted in 2013-07-12,  发布年份 2013

【 摘 要 】

Background

Restless Legs Syndrome is very common in hemodialysis patients however there are no comparative studies assessing the effectiveness of a non-pharmacological treatment to a classical treatment on parameters related to syndromes’ severity and quality of life.

Methods

In this randomized, partially double blind, placebo controlled trial, thirty two hemodialysis patients with restless legs syndrome were randomly assigned into three groups: 1) the exercise training group (N = 16), 2) the dopamine agonists group (ropinirole 0.25 mg/d) (N = 8) and 3) the placebo group (N = 8). The intervention programs lasted 6 months. Restless Legs Syndrome severity was assessed using the international severity scale, physical performance by a battery of tests, muscle size and composition by computed tomography, body composition by Dual Energy X Ray Absorptiometry, while depression score, sleep quality, daily sleepiness and quality of life were assessed through questionnaires.

Results

Exercise training and dopamine agonists were effective in reducing syndrome’s symptoms by 46% (P = 0.009) and 54% (P = 0.001) respectively. Within group changes revealed that both approaches significantly improved quality of life (P < 0.05), however, only the dopamine agonists significantly improved sleep quality (P = 0.009). Within group changes showed a tendency for lean body mass improvements with dopamine agonists, this reached statistical significance only with the exercise training (P = 0.014), which also reduced fat infiltration in muscles (P = 0.044) and improved physical performance (P > 0.05) in various tests. Between group changes detect significant improvements with both exercise and dopamine agonists in depression score (P = 0.003), while only the dopamine agonist treatment was able to significantly improve sleep quality, compared to exercise and placebo (P = 0.016).

Conclusions

A 6-month exercise training regime was as effective as a 6-month low dosage dopamine agonist treatment in reducing restless legs syndrome symptoms and improving depression score in uremic patients. Further research is needed in order to show whether a combination treatment could be more beneficial for the amelioration of RLS.

Trial registration

NCT00942253

【 授权许可】

   
2013 Giannaki et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 8.

【 参考文献 】

• [1]Murtagh FE, Addington-Hall J, Higginson IJ: The prevalence of symptoms in end-stage renal disease: a systematic review. Adv Chronic Kidney Dis 2007, 14(1):82-99.
• [2]Trenkwalder C, Hening WA, Montagna P, Oertel WH, Allen RP, Walters AS, Costa J, Stiasny-Kolster K, Sampaio C: Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov Disord 2008, 23(16):2267-2302.
• [3]Trenkwalder C, Stiasny K, Pollmacher T, Wetter T, Schwarz J, Kohnen R, Kazenwadel J, Kruger HP, Ramm S, Kunzel M, et al.: L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial. Sleep 1995, 18(8):681-688.
• [4]Pellecchia MT, Vitale C, Sabatini M, Longo K, Amboni M, Bonavita V, Barone P: Ropinirole as a treatment of restless legs syndrome in patients on chronic hemodialysis: an open randomized crossover trial versus levodopa sustained release. Clin Neuropharmacol 2004, 27(4):178-181.
• [5]Giannaki CD, Sakkas GK, Karatzaferi C, Hadjigeorgiou GM, Lavdas E, Liakopoulos V, Tsianas N, Koukoulis GN, Koutedakis Y, Stefanidis I: Evidence of increased muscle atrophy and impaired quality of life parameters in patients with uremic restless legs syndrome. PLoS One 2011, 6(10):e25180.
• [6]Johansen KL: Anabolic and catabolic mechanisms in end-stage renal disease. Adv Chronic Kidney Dis 2009, 16(6):501-510.
• [7]Garcia-Borreguero D, Allen RP, Benes H, Earley C, Happe S, Hogl B, Kohnen R, Paulus W, Rye D, Winkelmann J: Augmentation as a treatment complication of restless legs syndrome: concept and management. Mov Disord 2007, 22(S18):S476-S484.
• [8]Lou JS, Kearns G, Benice T, Oken B, Sexton G, Nutt J: Levodopa improves physical fatigue in Parkinson’s disease: a double-blind, placebo-controlled, crossover study. Mov Disord 2003, 18(10):1108-1114.
• [9]Giannaki CD, Sakkas GK, Hadjigeorgiou GM, Karatzaferi C, Patramani G, Lavdas E, Liakopoulos V, Koutedakis Y, Stefanidis I: Non-pharmacological management of periodic limb movements during hemodialysis session in patients with uremic restless legs syndrome. ASAIO J 2010, 56(6):538-542.
• [10]Sakkas GK, Hadjigeorgiou GM, Karatzaferi C, Maridaki MD, Giannaki CD, Mertens PR, Rountas C, Vlychou M, Liakopoulos V, Stefanidis I: Intradialytic aerobic exercise training ameliorates symptoms of restless legs syndrome and improves functional capacity in patients on hemodialysis: a pilot study. ASAIO J 2008, 54(2):185-190.
• [11]Allen RP, Picchietti D, Hening WA, Trenkwalder C, Walters AS, Montplaisi J: Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology: a report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health. Sleep Med 2003, 4(2):101-119.
• [12]Walters AS, LeBrocq C, Dhar A, Hening W, Rosen R, Allen RP, Trenkwalder C: Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 2003, 4(2):121-132.
• [13]Heyward VH: Assessing cardiorespiratory fitness. 3rd edition. Champaign IL, USA: Human Kinetics; 1998.
• [14]Mercer TH, Naish PF, Gleeson NP, Wilcock JE, Crawford C: Development of a walking test for the assessment of functional capacity in non-anaemic maintenance dialysis patients. Nephrol Dial Transplant 1998, 13(8):2023-2026.
• [15]Koufaki P, Mercer T: Assessment and monitoring of physical function for people with CKD. Adv Chronic Kidney Dis 2009, 16(6):410-419.
• [16]Lo JC, Mulligan K, Tai VW, Algren H, Schambelan M: “Buffalo hump” in men with HIV-1 infection. Lancet 1998, 351(9106):867-870.
• [17]Lo JC, Mulligan K, Noor MA, Lee GA, Schwarz JM, Grunfeld C, Schambelan M: The effects of low-dose growth hormone in HIV-infected men with fat accumulation: a pilot study. Clin Infect Dis 2004, 39(5):732-735.
• [18]Lee S, Kuk JL, Davidson LE, Hudson R, Kilpatrick K, Graham TE, Ross R: Exercise without weight loss is an effective strategy for obesity reduction in obese individuals with and without Type 2 diabetes. J Appl Physiol 2005, 99(3):1220-1225.
• [19]Kalantar-Zadeh K, Kopple JD, Block G, Humphreys MH: Association among SF36 quality of life measures and nutrition, hospitalization, and mortality in hemodialysis. J Am Soc Nephrol 2001, 12(12):2797-2806.
• [20]Zung WW: A self-rating depression scale. Arch Gen Psychiatry 1965, 12:63-70.
• [21]Johns MW: A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991, 14(6):540-545.
• [22]Daugirdas JT: Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 1993, 4(5):1205-1213.
• [23]Montagna P, Hornyak M, Ulfberg J, Hong SB, Koester J, Crespi G, Albrecht S: Randomized trial of pramipexole for patients with restless legs syndrome (RLS) and RLS-related impairment of mood. Sleep Med 2011, 12(1):34-40.
• [24]Aukerman MM, Aukerman D, Bayard M, Tudiver F, Thorp L, Bailey B: Exercise and restless legs syndrome: a randomized controlled trial. J Am Board Fam Med 2006, 19(5):487-493.
• [25]Fulda S, Wetter TC: Where dopamine meets opioids: a meta-analysis of the placebo effect in restless legs syndrome treatment studies. Brain 2008, 131(Pt 4):902-917.
• [26]Boecker H, Sprenger T, Spilker ME, Henriksen G, Koppenhoefer M, Wagner KJ, Valet M, Berthele A, Tolle TR: The runner’s high: opioidergic mechanisms in the human brain. Cereb Cortex 2008, 18(11):2523-2531.
• [27]Esteves AM, De Mello MT, Pradella-Hallinan M, Tufik S: Effect of acute and chronic physical exercise on patients with periodic leg movements. Med Sci Sports Exerc 2009, 41(1):237-242.
• [28]Von Spiczak S, Whone AL, Hammers A, Asselin MC, Turkheimer F, Tings T, Happe S, Paulus W, Trenkwalder C, Brooks DJ: The role of opioids in restless legs syndrome: an [11C]diprenorphine PET study. Brain 2005, 128(Pt 4):906-917.
• [29]Walters AS, Winkelmann J, Trenkwalder C, Fry JM, Kataria V, Wagner M, Sharma R, Hening W, Li L: Long-term follow-up on restless legs syndrome patients treated with opioids. Mov Disord 2001, 16(6):1105-1109.
• [30]Walters AS, Ondo WG, Zhu W, Le W: Does the endogenous opiate system play a role in the Restless Legs Syndrome? A pilot post-mortem study. J Neurol Sci 2009, 279(1–2):62-65.
• [31]Johansen KL: Exercise and chronic kidney disease: current recommendations. Sports Med 2005, 35(6):485-499.
• [32]Mafra D, Guebre-Egziabher F, Fouque D: Body mass index, muscle and fat in chronic kidney disease: questions about survival. Nephrol Dial Transplant 2008, 23(8):2461-2466.
• [33]Sakkas GK, Ball D, Mercer TH, Sargeant AJ, Tolfrey K, Naish PF: Atrophy of non-locomotor muscle in patients with end-stage renal failure. Nephrol Dial Transplant 2003, 18(10):2074-2081.
• [34]Sakkas GK, Sargeant AJ, Mercer TH, Ball D, Koufaki P, Karatzaferi C, Naish PF: Changes in muscle morphology in dialysis patients after 6 months of aerobic exercise training. Nephrol Dial Transplant 2003, 18(9):1854-1861.
• [35]Johansen KL, Painter PL, Sakkas GK, Gordon P, Doyle J, Shubert T: Effects of resistance exercise training and nandrolone decanoate on body composition and muscle function among patients who receive hemodialysis: a randomized, controlled trial. J Am Soc Nephrol 2006, 17(8):2307-2314.
• [36]Samuels ER, Hou RH, Langley RW, Szabadi E, Bradshaw CM: Comparison of pramipexole and modafinil on arousal, autonomic, and endocrine functions in healthy volunteers. J Psychopharmacol 2006, 20(6):756-770.
• [37]Sakkas GK, Kent-Braun JA, Doyle JW, Shubert T, Gordon P, Johansen KL: Effect of diabetes mellitus on muscle size and strength in patients receiving dialysis therapy. Am J Kidney Dis 2006, 47(5):862-869.
• [38]Machann J, Haring H, Schick F, Stumvoll M: Intramyocellular lipids and insulin resistance. Diabetes Obes Metab 2004, 6(4):239-248.
• [39]Thamer C, Machann J, Bachmann O, Haap M, Dahl D, Wietek B, Tschritter O, Niess A, Brechtel K, Fritsche A, et al.: Intramyocellular lipids: anthropometric determinants and relationships with maximal aerobic capacity and insulin sensitivity. J Clin Endocrinol Metab 2003, 88(4):1785-1791.
• [40]Mak RH: Impact of end-stage renal disease and dialysis on glycemic control. Semin Dial 2000, 13(1):4-8.
• [41]Sakkas GK, Karatzaferi C, Zintzaras E, Giannaki CD, Liakopoulos V, Lavdas E, Damani E, Liakos N, Fezoulidis I, Koutedakis Y, et al.: Liver fat, visceral adiposity, and sleep disturbances contribute to the development of insulin resistance and glucose intolerance in nondiabetic dialysis patients. Am J Physiol Regul Integr Comp Physiol 2008, 295(6):R1721-R1729.
• [42]Weisbord SD, Kimmel PL: Health-related quality of life in the era of erythropoietin. Hemodial Int 2008, 12(1):6-15.
• [43]Montplaisir J, Karrasch J, Haan J, Volc D: Ropinirole is effective in the long-term management of restless legs syndrome: a randomized controlled trial. Mov Disord 2006, 21(10):1627-1635.
• [44]Kawauchi A, Inoue Y, Hashimoto T, Tachibana N, Shirakawa S, Mizutani Y, Ono T, Miki T: Restless legs syndrome in hemodialysis patients: health-related quality of life and laboratory data analysis. Clin Nephrol 2006, 66(6):440-446.
• [45]Kimmel PL, Peterson RA: Depression in patients with end-stage renal disease treated with dialysis: has the time to treat arrived? Clin J Am Soc Nephrol 2006, 1(3):349-352.
• [46]Gigli GL, Adorati M, Dolso P, Piani A, Valente M, Brotini S, Budai R: Restless legs syndrome in end-stage renal disease. Sleep Med 2004, 5(3):309-315.