McArdle Disease Treatment by Ketogenic Diet

NCT04292938 | Completed DMC

• 1 other identifier: 543
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

McArdle's disease or Glycogen storage disease type 5 (GSD5), the most common muscle glycogenosis, is a rare disabling condition with no effective treatment. There are indications that a special dietary regimen could positively influence the disease manifestations. After contradictory indications for protein rich vs carbohydrate rich diets, several preliminary studies and more and more patients own experiences are now pointing to a low carbohydrate ketogenic diet (LCKD) as possibly effective in improving exercise tolerance and reducing muscle damage. The investigators propose a multicentre randomized single blind controlled trial testing efficacy of an individualized LCKD in GSD5. The investigators will test the ability of a 6 months dietary regimen with a 3:1 LCKD inducing a BOHB blood concentration of 1.5-4 mmol/l to improve the aerobic capacity as measured by peak VO2 at exercise testing in GSD5 patients. Thirty molecularly defined MCA adults will be enrolled: to half of them randomly selected the dietary regimen will be prescribed, while subjects in the control group will follow their usual balanced diet. The evaluators will be blinded to the diet followed by the examined patient

Conditions

Glycogen Storage Disease

Keywords

McArdle; Diet; Ketogenic

Outcome Measures

Primary Outcomes (1)

• Change in maximal (peak) oxidative capacity (VO2max)

  pre to post diet comparison of maximal O2 consumption attained during an incremental cycle ergometer test

  six months

Secondary Outcomes (7)

• heart rate

  six months

• maximal workload

  six months

• 12 min walking test

  six months

• Fatigue

  six months

• Short Form 36 (SF36)

  six months

Study Arms (2)

Ketogenic diet

ACTIVE COMPARATOR

patients will follow a low carbohydrate high lipid personalized diet causing blood BOHB level to be between 1.5-4 mmol/l for six months

Dietary Supplement: Low carbohydrate ketogenic diet

control group

NO INTERVENTION

Patients will be asked to maintain their usual dietary regimen

Interventions

Low carbohydrate ketogenic diet DIETARY_SUPPLEMENT

Dietary modification, including the use of supplements, with the aim of reaching a lipid/carbohydrate-protein 3:1 ratio with a minimum 1g/Kg/die in protein

Also known as: Ketogenic

Ketogenic diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• molecularly defined Glycogen storage disease type 5, ability to perform a cycle ergometer exercise test

You may not qualify if:

• pregnancy,
• medical condition preventing a LCKD regimen (CPT2 or acyl-CoA deficiency, liver heart or kidney failure, unstable diabetes).

Sponsors & Collaborators

• IRCCS Eugenio Medea: lead
• University of Pisa: collaborator
• University of Messina: collaborator

Study Sites (1)

IRCCS Medea

Conegliano, Treviso, 31015, Italy

Location

Related Publications (8)

• Quinlivan R, Martinuzzi A, Schoser B. Pharmacological and nutritional treatment for McArdle disease (Glycogen Storage Disease type V). Cochrane Database Syst Rev. 2014 Nov 12;2014(11):CD003458. doi: 10.1002/14651858.CD003458.pub5.

  PMID: 25391139 RESULT

• Busch V, Gempel K, Hack A, Muller K, Vorgerd M, Lochmuller H, Baumeister FA. Treatment of glycogenosis type V with ketogenic diet. Ann Neurol. 2005 Aug;58(2):341. doi: 10.1002/ana.20565. No abstract available.

  PMID: 16049943 RESULT

• Vorgerd M, Zange J. Treatment of glycogenosys type V (McArdle disease) with creatine and ketogenic diet with clinical scores and with 31P-MRS on working leg muscle. Acta Myol. 2007 Jul;26(1):61-3.

  PMID: 17915573 RESULT

• Cai QY, Zhou ZJ, Luo R, Gan J, Li SP, Mu DZ, Wan CM. Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. World J Pediatr. 2017 Dec;13(6):528-536. doi: 10.1007/s12519-017-0053-2. Epub 2017 Jul 12.

  PMID: 28702868 RESULT

• Muzykewicz DA, Lyczkowski DA, Memon N, Conant KD, Pfeifer HH, Thiele EA. Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy. Epilepsia. 2009 May;50(5):1118-26. doi: 10.1111/j.1528-1167.2008.01959.x. Epub 2009 Feb 12.

  PMID: 19220406 RESULT

• Roehl K, Sewak SL. Practice Paper of the Academy of Nutrition and Dietetics: Classic and Modified Ketogenic Diets for Treatment of Epilepsy. J Acad Nutr Diet. 2017 Aug;117(8):1279-1292. doi: 10.1016/j.jand.2017.06.006.

  PMID: 28754198 RESULT

• Paoli A, Bianco A, Damiani E, Bosco G. Ketogenic diet in neuromuscular and neurodegenerative diseases. Biomed Res Int. 2014;2014:474296. doi: 10.1155/2014/474296. Epub 2014 Jul 3.

  PMID: 25101284 RESULT

• Martinuzzi A, Musumeci O, Stefan C, Vinante E, Ferrati A, Perillo C, Pesenti N, Toscano A. Low-carbohydrate ketogenic diet in Mc Ardle's disease: a single-blinded randomized controlled trial. J Neurol. 2025 Oct 15;272(10):698. doi: 10.1007/s00415-025-13405-5.

  PMID: 41094169 DERIVED

MeSH Terms

Conditions

Glycogen Storage Disease

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Andrea Martinuzzi, MD, PhD

  IRCCS E Medea

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The assessors will be blinded as to the dietary regimen followed by the patient
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomised controlled single blind

Study Record Dates

• First Submitted: February 28, 2020
• First Posted: March 3, 2020
• Study Start: March 25, 2019
• Primary Completion: December 31, 2020
• Study Completion: June 30, 2021
• Last Updated: August 26, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)