Clinically Isolated Syndrome and Relapsing-Remitting Multiple Sclerosis

• ClinicalTrials.gov Identifier: NCT04009005
• Recruitment Status: Recruiting
• First Posted: July 5, 2019
• Last Update Posted: November 16, 2020
• Sponsor: Terry L. Wahls
• Information provided by (Responsible Party): Terry L. Wahls, University of Iowa

Tracking Information

• First Submitted Date: July 1, 2019
• First Posted Date: July 5, 2019
• Last Update Posted Date: November 16, 2020
• Actual Study Start Date: May 1, 2020
• Estimated Primary Completion Date: January 1, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 3, 2019)

• MS 54 Quality of Life scale physical health score [ Time Frame: change from baseline to 12 months ]
  Composite scores for physical health subscales
• MS 54 Quality of Life scale mental health score [ Time Frame: change from baseline to 12 months ]
  Composite scores for mental health subscales

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 12, 2020)

• Anxiety Score -Hospital Anxiety and Depression Survey [ Time Frame: change from baseline to 12 months ]
  Survey asking about mood and daily activities. Change in anxiety score for the hospital anxiety and depression scale score based on the responses.
• Depression score -Hospital Anxiety and Depression Survey [ Time Frame: change from baseline to 12 months ]
  Survey asking about mood and daily activities. Change in depress score for the hospital anxiety and depression scale score based on the responses.

Original Secondary Outcome Measures (submitted: July 3, 2019)

• Motor function walking endurance [ Time Frame: change from baseline to 12 months ]
  Distance in meters walked in 6 minutes;
• Motor function Hand coordination [ Time Frame: change from baseline to 12 months ]
  The time in seconds it takes complete 9 hole peg board test
• Motor function walking speed [ Time Frame: change from baseline to 12 months ]
  The number of seconds it takes to walk 25 feet
• Anxiety Score -Hospital Anxiety and Depression Survey [ Time Frame: change from baseline to 12 months ]
  Survey asking about mood and daily activities. Change in anxiety score for the hospital anxiety and depression scale score based on the responses.
• Depression score -Hospital Anxiety and Depression Survey [ Time Frame: change from baseline to 12 months ]
  Survey asking about mood and daily activities. Change in depress score for the hospital anxiety and depression scale score based on the responses.
• New Lesions on MRI [ Time Frame: Change from baseline to 12 months ]
  Number of new lesions using non contrast research MRI.
• Brain Volume MRI [ Time Frame: Change from baseline to 12 months ]
  Brain volume using non contrast research MRI.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinically Isolated Syndrome and Relapsing-Remitting Multiple Sclerosis
• Official Title: Clinically Isolated Syndrome and Relapsing-Remitting Multiple Sclerosis

Brief Summary

A key question in efforts to reduce symptoms and improve quality of life for multiple sclerosis (MS) patients is whether a therapeutic lifestyle (diet, stress reduction and exercise) is inferior to disease-modifying drug treatments in terms of reducing multiple sclerosis related symptoms, improving function and quality of life, and reducing the number of acute inflammatory lesions and loss of brain volume. This study will prospectively assess the changes in quality of life and clinical outcomes in two cohorts of patients who are recently diagnosed with clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) to begin answering that question.

The goal of this project is to compare a diet and therapeutic lifestyle only treatment usual care in the setting of newly diagnosed individuals with RRMS or CIS, which is the precursor to the development of MS.

Detailed Description

The goal of this project is to compare a diet and therapeutic lifestyle only treatment usual care in the setting of newly diagnosed individuals with RRMS or CIS, which is the precursor to the development of MS. The current standard of care typically includes disease-modifying drug treatment at the initial diagnosis of RRMS or CIS. Many patients are interested in adopting a therapeutic lifestyle as their initial approach to either RRMS or CIS. Some patients decline drug therapy due to high costs and or concerns about potential medication adverse events. There are no known scientific studies that have prospectively assessed outcomes for newly-diagnosed patients who decline disease-modifying drug treatment and instead utilized only a therapeutic diet and lifestyle to manage their MS-related symptoms. This study will prospectively investigate the effect of a therapeutic diet and lifestyle on quality of life, motor, cognitive and visual function, and brain structure in patients who have been trained and supported by the study team to utilize therapeutic diet and lifestyle to optimize neuronal health and those who are receiving usual care.

Our initial pilot study in the setting of progressive MS included diet and targeted supplements, stress reduction, exercise, and electrical stimulation of muscles and demonstrated significant reduction in fatigue, improvement in quality of life and improved mood and cognition. Subsequent pilot studies which utilized a diet-only intervention in the setting of RRMS demonstrated improved quality of life and improved walking and hand function.

Intervention arm:

This study will again utilize a multimodal approach, a low-lectin modified Paleolithic diet, stress reduction (breathing meditation exercise) and an exercise (daily walking and three times a week body weight strengthening) program in the absence of drug disease modifying treatment and targeted supplements in the intervention arm. The control arm will receive usual care.

Supplements (intervention arm only) Participants will be asked to continue taking any dietary supplements they report at beginning of study with the exception of supplements that are similar to those they will be taking as part of the study which they will be asked to discontinue and replace with study-approved brands (2 grams of fish oil, 1000 mcg methylB12 , 400 mcg methyl folate, pyridoxine 1.5 mg and N acetylcysteine 500 mg per day, and 2000 IU vitamin D3 .

The study will use videos from a three day seminar that teaches the public how to utilize a therapeutic diet and lifestyle to improve cellular physiology which may favorably impact disease progression to educate study participants. A registered dietitian with training in motivational interviewing and health coaching will call participants to provide coaching and support to participants as they adopt the study diet, breathing meditation and exercise program and begin the study supplements. The study coordinator and or registered dietitian will moderate monthly support group video conference meetings for participants in the intervention arm. The control arm will receive a monthly text/ email providing a summary to a recently published clinical trial related to multiple sclerosis / clinically isolated syndrome patients that is not related to diet quality or use of a therapeutic diet or lifestyle.

AIMS Aim 1: To assess the magnitude of change in perceived quality of life over 12 months in newly-diagnosed, disease modifying drug treatment naïve RRMS or CIS patients within and between two groups. Group one will receive standard of care. Group two will receive a therapeutic diet and lifestyle intervention that is taught and supported virtually.

• Study Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Comparison of the intervention arm to standard of care.

Masking: Single (Outcomes Assessor)
Masking Description:

Outcome assessor blinded to study arm.

Primary Purpose: Treatment

Condition

• Clinically Isolated Syndrome
• Relapsing Remitting Multiple Sclerosis

Intervention

Behavioral: Therapeutic diet and lifestyle

Educational videos, 4 individual support calls and monthly support group meetings conducted via an internet based audio/ video conference platform. Patients will be trained on a low lectin modified paleolithic diet; breathing meditation practice, and body weight strengthening

Study Arms

• No Intervention: Usual care
  Participants will receive usual care from their treating neurologist
• Experimental: Therapeutic Lifestyle
  Participants will be trained via videos from a three day in-person seminar that teaches the public about the use of a therapeutic diet and lifestyle to reduce multiple sclerosis related fatigue and improve quality of life.
  Intervention: Behavioral: Therapeutic diet and lifestyle

Publications *

• Bisht B, Darling WG, Grossmann RE, Shivapour ET, Lutgendorf SK, Snetselaar LG, Hall MJ, Zimmerman MB, Wahls TL. A multimodal intervention for patients with secondary progressive multiple sclerosis: feasibility and effect on fatigue. J Altern Complement Med. 2014 May;20(5):347-55. doi: 10.1089/acm.2013.0188. Epub 2014 Jan 29.
• Wahls TL, Reese D, Kaplan D, Darling WG. Rehabilitation with neuromuscular electrical stimulation leads to functional gains in ambulation in patients with secondary progressive and primary progressive multiple sclerosis: a case series report. J Altern Complement Med. 2010 Dec;16(12):1343-9. doi: 10.1089/acm.2010.0080.
• Reese D, Shivapour ET, Wahls TL, Dudley-Javoroski SD, Shields R. Neuromuscular electrical stimulation and dietary interventions to reduce oxidative stress in a secondary progressive multiple sclerosis patient leads to marked gains in function: a case report. Cases J. 2009 Aug 10;2:7601. doi: 10.4076/1757-1626-2-7601.
• Bisht B, Darling WG, Shivapour ET, Lutgendorf SK, Snetselaar LG, Chenard CA, Wahls TL. Multimodal intervention improves fatigue and quality of life in subjects with progressive multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2015;5:19-35. doi: 10.2147/DNND.S76523. Epub 2015 Feb 27. Erratum in: Degener Neurol Neuromuscul Dis. 2015 Sep 10;5:91.
• Irish AK, Erickson CM, Wahls TL, Snetselaar LG, Darling WG. Randomized control trial evaluation of a modified Paleolithic dietary intervention in the treatment of relapsing-remitting multiple sclerosis: a pilot study. Degener Neurol Neuromuscul Dis. 2017 Jan 4;7:1-18. doi: 10.2147/DNND.S116949. eCollection 2017.
• Lee JE, Bisht B, Hall MJ, Rubenstein LM, Louison R, Klein DT, Wahls TL. A Multimodal, Nonpharmacologic Intervention Improves Mood and Cognitive Function in People with Multiple Sclerosis. J Am Coll Nutr. 2017 Mar-Apr;36(3):150-168. doi: 10.1080/07315724.2016.1255160. Epub 2017 Apr 10.
• Wahls TL, Chenard CA, Snetselaar LG. Review of Two Popular Eating Plans within the Multiple Sclerosis Community: Low Saturated Fat and Modified Paleolithic. Nutrients. 2019 Feb 7;11(2). pii: E352. doi: 10.3390/nu11020352. Review.
• Chenard CA, Rubenstein LM, Snetselaar LG, Wahls TL. Nutrient Composition Comparison between a Modified Paleolithic Diet for Multiple Sclerosis and the Recommended Healthy U.S.-Style Eating Pattern. Nutrients. 2019 Mar 1;11(3). pii: E537. doi: 10.3390/nu11030537.
• Fellows Maxwell K, Wahls T, Browne RW, Rubenstein L, Bisht B, Chenard CA, Snetselaar L, Weinstock-Guttman B, Ramanathan M. Lipid profile is associated with decreased fatigue in individuals with progressive multiple sclerosis following a diet-based intervention: Results from a pilot study. PLoS One. 2019 Jun 18;14(6):e0218075. doi: 10.1371/journal.pone.0218075. eCollection 2019.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 3, 2019): 60
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: January 1, 2027
• Estimated Primary Completion Date: January 1, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• 1) A diagnosis of clinically isolated syndrome (CIS) or relapsing-remitting multiple sclerosis (RRMS) or CIS according to the 2010 McDonald's criteria, confirmed by the treating neurologist within 12 months of completing the first study visit.2) Must consent to sharing the clinical notes from their primary care and neurology providers during the study period.3) Must reside within the lower 48 states within the United States.4) Agreement by the treating neurologist that the patient may enroll in the study.

Exclusion Criteria:

1) Moderate or severe mental impairment as measured by the Short Portable Mental Health Questionnaire. 2) Presence of a contraindication to completing a brain MRI or having claustrophobia which interferes with completion of MRI studies without the use of sedation. 3) Taking insulin or Coumadin® medication. 4) History of oxalate kidney stones, schizophrenia, or active diagnosis of eating disorder. 5) Greater than 12 months since initial diagnosis of RRMS or CIS and first study visit.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mary Ehlinger, BA; 319 384 5002; mary-ehlinger@uiowa.edu

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04009005
• Other Study ID Numbers: 201908778
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: Terry L. Wahls, University of Iowa
• Study Sponsor: Terry L. Wahls
• Collaborators: Not Provided

Investigators

• Principal Investigator: Terry L Wahls, MD; University of Iowa

• PRS Account: University of Iowa
• Verification Date: November 2020