Efficacy of L-carnitine Versus Placebo in the Treatment of Fatigue in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— FACTSEP  

Official title:

A Randomised, Double Blinded Cross-over Study Comparing the Efficacy of L-carnitine Versus Placebo in the Treatment of Fatigue in Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01149525
• Other study ID #: CHUBX 2009/13
• Status: Completed
• Phase: Phase 3
• First received: June 21, 2010
• Last updated: May 5, 2017
• Start date: June 2010
• Est. completion date: July 2013

Study information

• Verified date: May 2017
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objective of this study is to evaluate the efficacy of L-carnitine versus placebo in the treatment of fatigue in multiple sclerosis patients. This study will randomize 60 patients in a cross-over design. This study is sponsored by academic French health institutions.

Description:

Fatigue is one of the most frequent disabling symptom in Multiple Sclerosis (MS). L-Carnitine is currently used in the symptomatic treatment of fatigue after chemotherapy in patients with cancers. It is also empirically used by numerous MS centers in the treatment of fatigue. However, this practice is not evidence-based (Cochrane review 2010). This study will evaluate the efficacy of L-carnitine versus placebo in the treatment of fatigue in MS patients in a randomized double blind national multicenter cross-over trial.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: July 2013
• Est. primary completion date: March 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years old and older

• Relapsing remitting (RR) secondary progressive (SP) or primary progressive multiple sclerosis according to McDonald 2005 (Polman) MS diagnostic criteria.

• Affected of fatigue for more than 3 months with global score on Modified Fatigue Impact Scale (MFIS)>45.

• Indication of treatment of fatigue to the appreciation of the neurologist.

• Expanded Disability Status Scale (EDSS) not exceeding 6.0.

• Information and comprehensive agreement signed by patient and the investigator.

• Subject affiliated to health insurance coverage.

Exclusion Criteria:

• Patients with serious unstable disease :

• recurrent or serious relapses

• rapidly ongoing disability impairment in the preceding 6 months

• serious or non stabilized depression

• Patients starting a new disease modifying therapy, immunosuppression or antidepressant therapy less than 3 months ago or not stabilized.

• Patients with a treatment of fatigue or of other condition that may interfere with fatigue evaluation to the appreciation of the neurologist.

• Energy drinks consumption or toxicomania.

• All other reasons to the opinion of the neurologist that may impair study management, especially patient compliance, neuro-psychological disorders that may input questionnaires filling.

• Person under protection of the law.

• Participation in other clinical trials (allowing for exceptions, after recommendation from the scientific council).

Related Conditions & MeSH terms

• Fatigue
• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• L-Carnitine
2g oral solution , twice per day (morning/evening), during 3 months
• Placebo
oral solution, twice per day (morning/evening), during 3 months

Locations

Country	Name	City	State
France	University Hospital, Hospital Pellegrin	Bordeaux
France	University Hospital	Fort de France
France	University Hospital, Hospital Dupuytren	Limoges
France	University Hospital, Hospital Central	Nancy
France	University Hospital, Hospital Laënnec	Nantes
France	University Hospital, Hospital Pasteur	Nice

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

References & Publications (27)

Bakshi R. Fatigue associated with multiple sclerosis: diagnosis, impact and management. Mult Scler. 2003 Jun;9(3):219-27. Review. — View Citation

Cruciani RA, Dvorkin E, Homel P, Culliney B, Malamud S, Shaiova L, Fleishman S, Lapin J, Klein E, Lesage P, Portenoy R, Esteban-Cruciani N. L-carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Ann N Y Acad Sci. 2004 Nov;1033:168-76. — View Citation

Cruciani RA, Dvorkin E, Homel P, Malamud S, Culliney B, Lapin J, Portenoy RK, Esteban-Cruciani N. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. J Pain Symptom Manage. 2006 Dec;32(6):551-9. — View Citation

Debouverie M, Pittion S. [Fatigue and episodic exhaustion as a feature of multiple sclerosis]. Rev Neurol (Paris). 2006 Mar;162(3):295-7. French. — View Citation

Debouverie M, Pittion-Vouyovitch S, Louis S, Guillemin F. Validity of a French version of the fatigue impact scale in multiple sclerosis. Mult Scler. 2007 Sep;13(8):1026-32. — View Citation

Filippi M, Rocca MA, Colombo B, Falini A, Codella M, Scotti G, Comi G. Functional magnetic resonance imaging correlates of fatigue in multiple sclerosis. Neuroimage. 2002 Mar;15(3):559-67. — View Citation

Gramignano G, Lusso MR, Madeddu C, Massa E, Serpe R, Deiana L, Lamonica G, Dessì M, Spiga C, Astara G, Macciò A, Mantovani G. Efficacy of l-carnitine administration on fatigue, nutritional status, oxidative stress, and related quality of life in 12 advanced cancer patients undergoing anticancer therapy. Nutrition. 2006 Feb;22(2):136-45. — View Citation

Graziano F, Bisonni R, Catalano V, Silva R, Rovidati S, Mencarini E, Ferraro B, Canestrari F, Baldelli AM, De Gaetano A, Giordani P, Testa E, Lai V. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients. Br J Cancer. 2002 Jun 17;86(12):1854-7. — View Citation

GRIZZLE JE. THE TWO-PERIOD CHANGE-OVER DESIGN AN ITS USE IN CLINICAL TRIALS. Biometrics. 1965 Jun;21:467-80. — View Citation

Kieser M, Friede T. Re-calculating the sample size in internal pilot study designs with control of the type I error rate. Stat Med. 2000 Apr 15;19(7):901-11. — View Citation

Krupp LB, Coyle PK, Doscher C, Miller A, Cross AH, Jandorf L, Halper J, Johnson B, Morgante L, Grimson R. Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo. Neurology. 1995 Nov;45(11):1956-61. — View Citation

Lebrun C, Alchaar H, Candito M, Bourg V, Chatel M. Levocarnitine administration in multiple sclerosis patients with immunosuppressive therapy-induced fatigue. Mult Scler. 2006 Jun;12(3):321-4. — View Citation

Montel SR, Bungener C. Coping and quality of life in one hundred and thirty five subjects with multiple sclerosis. Mult Scler. 2007 Apr;13(3):393-401. Epub 2007 Jan 29. — View Citation

Neri S, Pistone G, Saraceno B, Pennisi G, Luca S, Malaguarnera M. L-carnitine decreases severity and type of fatigue induced by interferon-alpha in the treatment of patients with hepatitis C. Neuropsychobiology. 2003;47(2):94-7. — View Citation

Oken BS, Kishiyama S, Zajdel D, Bourdette D, Carlsen J, Haas M, Hugos C, Kraemer DF, Lawrence J, Mass M. Randomized controlled trial of yoga and exercise in multiple sclerosis. Neurology. 2004 Jun 8;62(11):2058-64. — View Citation

Pittion-Vouyovitch S, Debouverie M, Guillemin F, Vandenberghe N, Anxionnat R, Vespignani H. Fatigue in multiple sclerosis is related to disability, depression and quality of life. J Neurol Sci. 2006 Apr 15;243(1-2):39-45. Epub 2006 Jan 24. — View Citation

Plioplys AV, Plioplys S. Amantadine and L-carnitine treatment of Chronic Fatigue Syndrome. Neuropsychobiology. 1997;35(1):16-23. — View Citation

Plioplys AV, Plioplys S. Serum levels of carnitine in chronic fatigue syndrome: clinical correlates. Neuropsychobiology. 1995;32(3):132-8. — View Citation

Pucci E, Branãs P, D'Amico R, Giuliani G, Solari A, Taus C. Amantadine for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD002818. Review. — View Citation

Rebouche CJ. Kinetics, pharmacokinetics, and regulation of L-carnitine and acetyl-L-carnitine metabolism. Ann N Y Acad Sci. 2004 Nov;1033:30-41. Review. — View Citation

Richardson BA, Flack VF. The analysis of incomplete data in the three-period two-treatment cross-over design for clinical trials. Stat Med. 1996 Jan 30;15(2):127-43. — View Citation

Stankoff B, Waubant E, Confavreux C, Edan G, Debouverie M, Rumbach L, Moreau T, Pelletier J, Lubetzki C, Clanet M; French Modafinil Study Group.. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Neurology. 2005 Apr 12;64(7):1139-43. — View Citation

Taglialatela G, Navarra D, Cruciani R, Ramacci MT, Alemà GS, Angelucci L. Acetyl-L-carnitine treatment increases nerve growth factor levels and choline acetyltransferase activity in the central nervous system of aged rats. Exp Gerontol. 1994 Jan-Feb;29(1):55-66. — View Citation

Tejani AM, Wasdell M, Spiwak R, Rowell G, Nathwani S. Carnitine for fatigue in multiple sclerosis. Cochrane Database Syst Rev. 2010 Feb 17;(2):CD007280. doi: 10.1002/14651858.CD007280.pub2. Review. Update in: Cochrane Database Syst Rev. 2012;5:CD007280. — View Citation

Tomassini V, Pozzilli C, Onesti E, Pasqualetti P, Marinelli F, Pisani A, Fieschi C. Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. J Neurol Sci. 2004 Mar 15;218(1-2):103-8. — View Citation

van Diemen HA, Polman CH, van Dongen TM, van Loenen AC, Nauta JJ, Taphoorn MJ, van Walbeek HK, Koetsier JC. The effect of 4-aminopyridine on clinical signs in multiple sclerosis: a randomized, placebo-controlled, double-blind, cross-over study. Ann Neurol. 1992 Aug;32(2):123-30. — View Citation

Wingerchuk DM, Benarroch EE, O'Brien PC, Keegan BM, Lucchinetti CF, Noseworthy JH, Weinshenker BG, Rodriguez M. A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis. Neurology. 2005 Apr 12;64(7):1267-9. — View Citation

* Note: There are 27 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global score on the 21 item Modified Fatigue Impact Scale (MFIS, translated and validated in French).		Three months and nine months (2 periods of 3 months on treatment/placebo separated by a wash-out period of 3 months)
Secondary	Fatigue Severity Scale (FSS)		Three and nine months
Secondary	Fatigue Visual Analogic Scale (VAS)		Three and nine months
Secondary	physical dimension scale of MFIS		Three and nine months
Secondary	SEP59 scale of quality of life (Multiple Sclerosis Quality Of Life scale validated in french)		Three and nine months