Dataset Information

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.

ABSTRACT:

Background

Dietary changes impact human physiology and immune function and have potential as therapeutic strategies.

Objective

Assess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics.

Methods

Sixty-five subjects with relapsing MS enrolled into a 6-month prospective, intention-to-treat KD intervention. Adherence was monitored with daily urine ketone testing. At baseline, fatigue, depression and quality of life (QoL) scores were obtained in addition to fasting adipokines and MS-related clinical outcome metrics. Baseline metrics were repeated at 3 and/or 6 months on-diet.

Results

Eighty-three percent of participants adhered to the KD for the study duration. Subjects exhibited significant reductions in fat mass and showed a nearly 50% decline in self-reported fatigue and depression scores. MS QoL physical health (67±16 vs 79±12, p<0.001) and mental health (71±17 vs 82±11, p<0.001) composite scores increased on-diet. Significant improvements were noted in Expanded Disability Status Scale scores (2.3±0.9 vs 1.9±1.1, p<0.001), 6-minute walk (1631±302 vs 1733±330 ft, p<0.001) and Nine-Hole Peg Test (21.5±3.6 vs 20.3±3.7 s, p<0.001). Serum leptin was lower (25.5±15.7 vs 14.0±11.7 ng/mL, p<0.001) and adiponectin was higher (11.4±7.8 vs 13.5±8.4 µg/mL, p=0.002) on the KD.

Conclusion

KDs are safe and tolerable over a 6-month study period and yield improvements in body composition, fatigue, depression, QoL, neurological disability and adipose-related inflammation in persons living with relapsing MS.

Trial registration information

Registered on ClinicalTrials.gov under registration number NCT03718247, posted on 24 October 2018. First patient enrolment date: 1 November 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

SUBMITTER: Brenton JN

PROVIDER: S-EPMC9350909 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.

Brenton J Nicholas JN Lehner-Gulotta Diana D Woolbright Emma E Banwell Brenda B Bergqvist A G Christina AGC Chen Shanshan S Coleman Rachael R Conaway Mark M Goldman Myla D MD

Journal of neurology, neurosurgery, and psychiatry 20220413 6

<h4>Background</h4>Dietary changes impact human physiology and immune function and have potential as therapeutic strategies.<h4>Objective</h4>Assess the tolerability of a ketogenic diet (KD) in patients with relapsing multiple sclerosis (MS) and define the impact on laboratory and clinical outcome metrics.<h4>Methods</h4>Sixty-five subjects with relapsing MS enrolled into a 6-month prospective, intention-to-treat KD intervention. Adherence was monitored with daily urine ketone testing. At baseli ...[more]

PMID: 35418509

Similar Datasets

Project description:BackgroundKetogenic diets (KDs) are safe and tolerable in people with multiple sclerosis (MS). While many patient-reported and clinical benefits are noted, the sustainability of these diets outside of a clinical trial is unknown.AimsEvaluate patient perceptions of the KD following intervention, determine the degree of adherence to KDs post-trial, and examine what factors increase the likelihood of KD continuation following the structured diet intervention trial.MethodsSixty-five subjects with relapsing MS previously enrolled into a 6-month prospective, intention-to-treat KD intervention. Following the 6-month trial, subjects were asked to return for a 3-month post-study follow-up, at which time patient reported outcomes, dietary recall, clinical outcome measures, and laboratory values were repeated. In addition, subjects completed a survey to evaluate sustained and attenuated benefits following completion of the intervention phase of the trial.ResultsFifty-two subjects (81%) returned for the 3-month post-KD intervention visit. Twenty-one percent reported continued adherence to a strict KD and an additional 37% reported adhering to a liberalized, less restrictive form of the KD. Those subjects with greater reductions in body mass index (BMI) and fatigue at 6-months on-diet were more likely to continue on KD following trial completion. Using intention-to-treat analysis, patient-reported and clinical outcomes at 3-months post-trial remained significantly improved from baseline (pre-KD), though the degree of improvement was slightly attenuated relative to outcomes at 6-months on KD. Regardless of diet type following the KD intervention, dietary patterns shifted toward greater protein and polyunsaturated fats and less carbohydrate/added sugar consumption.ConclusionsFollowing the 6-month KD intervention study, the majority of subjects elected to continue on KD, though many pursued a more liberal limit for carbohydrate restriction. Those who experienced a greater reduction in BMI or fatigue were more likely to continue with strict KD. The 6-month KD intervention induced persistent changes to dietary habits in the months following study completion.Trial registration informationRegistered on Clinicaltrials.gov under registration number NCT03718247, posted on Oct 24, 2018. First patient enrollment date: Nov 1, 2018. Link: https://clinicaltrials.gov/ct2/show/NCT03718247?term=NCT03718247&draw=2&rank=1.

Project description:IntroductionFingolimod 0.5 mg is an orally active sphingosine 1-phosphate receptor modulator approved for use in adults with relapsing multiple sclerosis (MS). The efficacy and safety profile of fingolimod has been well characterized in a large clinical development program. Here, we report the safety and tolerability of fingolimod in relapsing-remitting MS (RRMS) patients from Latin America.MethodsA total of 162 patients with RRMS, predominantly from Latin American countries (138/162), were enrolled in this 16-week, single treatment arm, open-label, multi-center study. Unlike the phase III pivotal studies, this study permitted enrollment of patients with controlled diabetes, certain cardiac and pulmonary conditions, older age, and higher baseline Expanded Disability Status Scale. All patients were monitored clinically for a minimum of 6 hours after the first dose. Safety and tolerability assessments were based on adverse events, clinically notable laboratory abnormalities, vital signs, ophthalmic examinations, and electrocardiograms.ResultsOverall, the safety and tolerability profile was consistent with that reported previously in phase 3 studies and the FIRST study. Adverse events (AEs) were predominantly mild (n = 49, 35.5%) or moderate (n = 27, 19.6%). Three patients (2.2%) discontinued fingolimod due to AEs. Infections were reported in 33 patients (23.9%) and were predominantly mild in nature (n = 28, 20.3%). Increases in alanine aminotransferase enzymes of ≥3, ≥5 and ≥10 upper limit of normal were reported in five (3.7%), three (2.2%) and one (0.7%) patients, respectively. Hypertension cases (n = 3; 2.2%) did not result in treatment discontinuation and were controlled with antihypertensive therapy. Following first-dose administration, the majority of patients (90.6%) were discharged at 6 h. During the first-dose monitoring, 5 cases of bradycardia were reported; none required extended monitoring or treatment for symptomatic bradycardia.ConclusionThe first dose of fingolimod 0.5 mg was well tolerated in RRMS patients from Latin America. The overall safety profile was clinically manageable and consistent with previous fingolimod studies.FundingNovartis.Trial registrationClinicalTrials.gov #NCT01497262.

Dataset Information

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.

Background

Objective

Methods

Results

Conclusion

Trial registration information

Publications

Phase II study of ketogenic diets in relapsing multiple sclerosis: safety, tolerability and potential clinical benefits.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets