Relapsing Remitting Multiple SclerosisNCT03718247
Utilization of the Ketogenic Diet in Patient With Relapsing Remitting MS
An observational study of Relapsing Remitting Multiple Sclerosis, run by University of Virginia at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 12 to 55 years
- Conditions the study is for
- Relapsing Remitting Multiple Sclerosis
- What is being tested?
- Modified Atkins diet
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Oct 2018to 1 Jul 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 55 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: Patients with relapsing-remitting MS
Who may be able to join
- Ability to provide informed consent (or assent for minors)
- Relapsing-remitting MS diagnosis per 2010 McDonald criteria
- On same Demyelinating Treatment for at least 6 months
- Ages ≥ 12 years to ≤ 45 years
Who cannot join
- Comorbid disease (including hypercholesterolemia, cardiovascular or renal disease) that would interfere with safety and/or study completion
- Current pregnancy or planning pregnancy
- Progressive form of MS
- Estimated GFR less than 45 mL/min based on a serum creatinine drawn within 30 days of enrollment
- Acute kidney injury
- History of paraproteinemia syndromes such as multiple myeloma
Show all 11Show fewer
- Hepatorenal syndrome
- Liver transplant
- Underweight or low weight patients as defined by:
- BMI value <20 for those 18 years and older
- <10th percentile for BMI by CDC growth charts for those less than 18 years of age
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Virginia
Charlottesville, Virginia, 22903
About this study
Official title: The Effect of the Ketogenic Diet on Patients With Relapsing Remitting Multiple Sclerosis
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.
Read the detailed 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.
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Being tested
- Modified Atkins diet
- Keywords
- Ketogenic diet
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Atkins dietOther
High fat low carbohydrate diet.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
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.
Measured: 12 months
Secondary outcomes (1)
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2018
- Study start31 Oct 2018
- Primary completion21 Jun 2021
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Relapsing Remitting Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, J. Nicholas Brenton, MD, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03718247
- Sponsor's protocol ID
- 20877
- Status last verified
- May 2022
- First submitted
- 16 Oct 2018
- Last updated
- 18 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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. doi: 10.1186/1471-2202-7-29.
PubMed 16584562Lassmann 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.
PubMed 23007702van 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.
PubMed 18930811Perlman J, Wetmore E, Lehner-Gulotta D, Banwell B, Bergqvist AGC, Coleman R, Chen S, Conaway M, Goldman MD, Morse AM, Brenton JN. Impact of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis. Sleep Med. 2024 Oct;122:213-220. doi: 10.1016/j.sleep.2024.08.020. Epub 2024 Aug 28.
PubMed 39208520Wetmore E, Lehner-Gulotta D, Florenzo B, Banwell B, Bergqvist AGC, Coleman R, Conaway M, Goldman MD, Brenton JN. Ketogenic diet in relapsing multiple sclerosis: Patient perceptions, post-trial diet adherence & outcomes. Clin Nutr. 2023 Aug;42(8):1427-1435. doi: 10.1016/j.clnu.2023.06.029. Epub 2023 Jul 4.
PubMed 37433230Oh U, Woolbright E, Lehner-Gulotta D, Coleman R, Conaway M, Goldman MD, Brenton JN. Serum neurofilament light chain in relapsing multiple sclerosis patients on a ketogenic diet. Mult Scler Relat Disord. 2023 May;73:104670. doi: 10.1016/j.msard.2023.104670. Epub 2023 Mar 25.
PubMed 36996634Brenton JN, Lehner-Gulotta D, Woolbright E, Banwell B, Bergqvist AGC, Chen S, Coleman R, Conaway M, Goldman MD. Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits. J Neurol Neurosurg Psychiatry. 2022 Jun;93(6):637-644. doi: 10.1136/jnnp-2022-329074. Epub 2022 Apr 13.
PubMed 35418509
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of the Ketogenic Diet on Patients With Relapsing Remitting Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT03718247
- Acronym / sponsor ID
- 20877
- Conditions
- Relapsing Remitting Multiple Sclerosis
- Keywords
- Ketogenic diet
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Study start
- 31 Oct 2018 (actual)
- Primary completion
- 21 Jun 2021 (actual)
- Study completion
- 1 Jul 2021 (actual)
- First posted
- 24 Oct 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 12 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- Patients with relapsing-remitting MS
Key inclusion criteria (4 listed)
- Ability to provide informed consent (or assent for minors)
- Relapsing-remitting MS diagnosis per 2010 McDonald criteria
- On same Demyelinating Treatment for at least 6 months
- Ages ≥ 12 years to ≤ 45 years
Key exclusion criteria (11 listed)
- Comorbid disease (including hypercholesterolemia, cardiovascular or renal disease) that would interfere with safety and/or study completion
- Current pregnancy or planning pregnancy
- Progressive form of MS
- Estimated GFR less than 45 mL/min based on a serum creatinine drawn within 30 days of enrollment
- Acute kidney injury
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modified Atkins dietHigh fat low carbohydrate diet. | Other | – |
Primary outcome
Diet Tolerability and compliance
Time frame: 6 months
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.
Diet Benefits
Time frame: 12 months
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.
1 secondary outcome
Physical changes
Time frame: 12 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2022.
- Background: PubMed 16584562Zhao 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. doi: 10.1186/1471-2202-7-29.
- Background: PubMed 23007702Lassmann 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.
- Background: PubMed 18930811van 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.
- Derived from this study: PubMed 39208520Perlman J, Wetmore E, Lehner-Gulotta D, Banwell B, Bergqvist AGC, Coleman R, Chen S, Conaway M, Goldman MD, Morse AM, Brenton JN. Impact of a ketogenic diet on sleep quality in people with relapsing multiple sclerosis. Sleep Med. 2024 Oct;122:213-220. doi: 10.1016/j.sleep.2024.08.020. Epub 2024 Aug 28.
- Derived from this study: PubMed 37433230Wetmore E, Lehner-Gulotta D, Florenzo B, Banwell B, Bergqvist AGC, Coleman R, Conaway M, Goldman MD, Brenton JN. Ketogenic diet in relapsing multiple sclerosis: Patient perceptions, post-trial diet adherence & outcomes. Clin Nutr. 2023 Aug;42(8):1427-1435. doi: 10.1016/j.clnu.2023.06.029. Epub 2023 Jul 4.
- Derived from this study: PubMed 36996634Oh U, Woolbright E, Lehner-Gulotta D, Coleman R, Conaway M, Goldman MD, Brenton JN. Serum neurofilament light chain in relapsing multiple sclerosis patients on a ketogenic diet. Mult Scler Relat Disord. 2023 May;73:104670. doi: 10.1016/j.msard.2023.104670. Epub 2023 Mar 25.
- Derived from this study: PubMed 35418509Brenton JN, Lehner-Gulotta D, Woolbright E, Banwell B, Bergqvist AGC, Chen S, Coleman R, Conaway M, Goldman MD. Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits. J Neurol Neurosurg Psychiatry. 2022 Jun;93(6):637-644. doi: 10.1136/jnnp-2022-329074. Epub 2022 Apr 13.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Relapsing Remitting Multiple Sclerosis, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diet Tolerability and compliance (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03718247, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 May 2022.