Utilization of the Ketogenic Diet in Patient With Relapsing Remitting MS

Relapsing Remitting Multiple Sclerosis Clinical Trial

Official title:

The Effect of the Ketogenic Diet on Patients With Relapsing Remitting Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03718247
• Other study ID #: 20877
• Status: Completed
• Start date: October 31, 2018
• Est. completion date: July 1, 2021

Study information

• Verified date: May 2022
• Source: University of Virginia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The purpose of this study is to evaluate the benefits of a low-carbohydrate, high-fat diet (ketogenic diet) in up to 50 subjects with relapsing-remitting multiple sclerosis (RRMS), a chronic neuro-inflammatory disease. The primary aim of this study is to provide evidence of tolerability of the ketogenic diet in patients with RRMS. The principal investigator hypothesizes that the diet may prove beneficial for participants disease state in multiple potential ways.The study consists of 5 visits over a 12 month period. During these visits subjects will undergo fasting lab work, micro-biome sampling, neurological testing, body composition analysis, meeting with dietitian, and will be asked to complete surveys as well as a diet recall log.

Description:

The purpose of this study is to see if a high fat, low carbohydrate diet is safe and how it effects post trial diet habits, physique, and disease course in patients with relapsing remitting multiple sclerosis. In particular, multiple sclerosis is a neurodegenerative disorder that is characterized by inflammation, microglial inflammation, and hypoxia in its relapsing-remitting form.1 One of the hypothesized therapeutic mechanisms of ketogenic diets is related to its effect on decreasing glycolysis, decreasing reactive oxygen species (ROS), and increasing ATP production by mitochondria. Production of ROS and macrophage activation have been directly correlated with demyelination and axonal injury in multiple sclerosis.2,3 In mouse models with experimental allergic encephalomyelitis (EAE), a model disease in mice that has many similar properties to that of MS in humans, experiments have demonstrated that impairment of memory and spatial learning are directly correlated with increased cytokine and chemokine expression and ROS production. In EAE mice fed a ketogenic diet, there were noted improvements in motor disability, memory dysfunction, and CNS inflammation - which on the whole are suggestive that a ketogenic diet may have a multitude of benefits in patients with multiple sclerosis.

The study goal is to recruit 50 young adult or adult patients with relapsing-remitting multiple sclerosis that show interest in starting and maintaining a ketogenic diet for six months. Prior to initiating the diet, the study team will characterize each patient's disease by analyzing multiple factors - including baseline expanded disability status scale (EDSS) and annualized relapse rates (ARR). Throughout the course of the 12 month study participants will be asked to complete several patient reported outcomes, an online food diary recall, and track their diet compliance using urinary ketone testing strips provided by the study daily.In addition, the study team will also draw serum lab work every 3 months that we anticipate may be affected by the diet (including hemoglobin A1C, lipid panel, and cytokine profiles). Rectal swabs will be requested during the study to look at effects of the diet on the microbiome both pre and post diet. Additionally, activity monitors (accelerometers) will be worn by each subject for 1 week prior to initiation of the diet to provide evidence of pre-diet activity levels and at various times throughout the study for comparison. Participating patients will receive education on starting, maintaining, and stopping the 6 month diet by a nutritionist. The nutritionist will meet with patients at scheduled office visits and will be available for questions during the duration of the patients participation. Subjects will also undergo anthropometric assessments with a bodpod used to measure body mass as well.

All measures will be compared with statistical analyses, utilizing both pre and post diet values to help determine benefit of the diet on various aspects of the patient's overall health and wellness.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: July 1, 2021
• Est. primary completion date: June 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years to 55 Years

Eligibility

Inclusion Criteria:

1. Ability to provide informed consent (or assent for minors)

2. Relapsing-remitting MS diagnosis per 2010 McDonald criteria

3. On same Demyelinating Treatment for at least 6 months

4. Ages = 12 years to = 45 years

Exclusion Criteria:

1. Comorbid disease (including hypercholesterolemia, cardiovascular or renal disease) that would interfere with safety and/or study completion

2. Current pregnancy or planning pregnancy

3. Progressive form of MS

4. Estimated GFR less than 45 mL/min based on a serum creatinine drawn within 30 days of enrollment

5. Acute kidney injury

6. History of paraproteinemia syndromes such as multiple myeloma

7. Hepatorenal syndrome

8. Liver transplant

9. Underweight or low weight patients as defined by:

1. BMI value <20 for those 18 years and older

2. <10th percentile for BMI by CDC growth charts for those less than 18 years of age

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Intervention

Other:
• Modified Atkins diet
High fat low carbohydrate diet.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
University of Virginia

Country where clinical trial is conducted

United States, 

References & Publications (3)

Lassmann H, van Horssen J, Mahad D. Progressive multiple sclerosis: pathology and pathogenesis. Nat Rev Neurol. 2012 Nov 5;8(11):647-56. doi: 10.1038/nrneurol.2012.168. Epub 2012 Sep 25. Review. — View Citation

van Horssen J, Schreibelt G, Drexhage J, Hazes T, Dijkstra CD, van der Valk P, de Vries HE. Severe oxidative damage in multiple sclerosis lesions coincides with enhanced antioxidant enzyme expression. Free Radic Biol Med. 2008 Dec 15;45(12):1729-37. doi: 10.1016/j.freeradbiomed.2008.09.023. Epub 2008 Oct 7. — View Citation

Zhao Z, Lange DJ, Voustianiouk A, MacGrogan D, Ho L, Suh J, Humala N, Thiyagarajan M, Wang J, Pasinetti GM. A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis. BMC Neurosci. 2006 Apr 3;7:29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Diet Tolerability and compliance	Determine if patients are able to adhere to (number of days patient able to demonstrate ketosis) and tolerate a strict diet over an extended period of time as reported in urinary ketone analysis.	6 months
Primary	Diet Benefits	Determine the benefits, if any, of the ketogenic diet in RRMS subjects physically, emotionally, and clinically as reported in patient reported outcome surveys. Survey responses are evaluated on a scale of 0-10 with 0 being no affect and 10 being highly affected by the disease.	12 months
Secondary	Physical changes	Assessment of height and weight to calculate subject BMI throughout the study. This will be compared with survey on physical activity to see if scores (no disease impact to high disease impact on activity) correspond with changes in BMI.	12 months