Safety and Tolerability of the Ketogenic Diet in ALS

Institutional Review Board, Hospital for Special Surgery

July 27, 2010

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Principal Investigator

Dale J. Lange, MD

Summary

This is an open label one arm study of ketogenic diet in patients with ALS. A total of 30 subjects will complete this study. We will enroll 30 patients with ALS with a functioning gastrostomy. The diet will totally consist of a nutritionally complete preparation that is specially formulated to contain 4 parts fat to 1 part protein/carbohydrate to produce maximal levels of ketones. Hydration status will be monitored. Safety will be measured by changes in weight. Weight loss is a common problem in patients with ALS. Weight will therefore be our primary endpoint and will be compared to established rates of weight loss in patients assigned to placebo groups in previous ALS therapeutic trials.
The study includes 24 weeks on the ketogenic diet and a follow-up visit 4 weeks after stopping the diet. It is anticipated that the entire study is to be completed within a period of 3 years. Patients wishing to continue on the ketogenic diet after 24 weeks may discuss this with their referring neurologist.

Inclusion/Exclusion Criteria

Inclusion Criteria

1. Familial or sporadic ALS diagnosed as probable, laboratory-supported probable or definite according to the World Federation of Neurology El Escorial criteria [37]
2. Age 18 or older
3. Capable of providing informed consent and complying with trial procedures
4. Gastrostomy tube in place for the prior month
5. Appel ALS score less than 100
6. Able to stand on a scale with assistance
7. For patients with Appel ALS scores greater than 80, availability of caregiver who is willing and able to:
 •Prepare, administer and log tube feeds
 •Check and log gastric residuals
 •Assist with weighing subject at home if necessary
8. Willing to chart formula intake during the six-month study
9. Patients either not taking Riluzole (Rilutek) or Minocycline or on a stable dose of these for 30 days
10. Not taking Coenzyme Q10 or on a stable dose and brand for 30 days
11. Absence of exclusion criteria

Exclusion Criteria

1. Forced vital capacity <50% of predicted
2. Dependence on mechanical ventilation for more than 12 hours per day
3. Exposure to any experimental agent within 30 days of onset of this protocol
4. Women who are pregnant or planning to become pregnant
5. Women of childbearing potential not practicing contraception
6. Enrollment in another research study within 30 days of or during this trial
7. Mini-Mental State Exam (MMSE) score <20
8. Patients with symptomatic cardiac disease or hypercholesterolemia
9. Patients with myocardial infarction within 6 months of this trial
10. Renal dysfunction defined as BUN and creatinine >2XULN
11. Known mitochondrial disease
12. BMI<18.5
13. Prior use of a 4:1 ketogenic diet or Atkins diet within 1 month of this trial
14. Impaired liver function, defined as AST or ALT of 3 X ULN
15. Patients who have a pacemaker or other internal electronic medical device

Contact Information

Mona Shahbazi, RN, OCN, MSN
shabbazim@hss.edu
212.774.2361