Translational Work & Clinical Trials

The John L. Trotter MS Center is committed to translating work done in the laboratory to the Clinic. Anne Cross, MD, directs a clinical trial that was initiated at this institution, based upon prior work in the laboratories at Washington University.

The trial studies the effect of B cells and their products on disease activity in MS patients. Patients in the study, who all have ongoing MS disease activity despite taking FDA-approved medications, are depleted of circulating B cells for six to 12 months using a highly specific chemotherapeutic agent. MS activity in the brain is monitored by MRI. The imaging results are being analyzed by Robert Naismith, MD.

Clinical trials

Mission

The John L. Trotter MS Center at Washington University is committed to patient care, research and teaching. Our research revolves around the following needs and unanswered questions:

  • What is the cause of MS?
  • Why do people get progressive MS?
  • What tools can we use in clinical practice to inform us about an individual’s disease severity, how to select the best treatment, and how to determine whether a therapy is working.
  • What new treatments can be developed to help with common MS symptoms?
  • What new treatments can reduce inflammation while balancing efficacy, safety, tolerability, and convenience?
  • What new treatments can repair the nervous system and how will we measure whether they are successful?
  • Can we prevent MS in someone at risk to develop it?
  • Can we cure MS in someone who already has it?

A critical partnership

We cannot answer these questions without your help. We have a commitment to make this disease better until we have a cure. Your participation is appreciated and vital. Your involvement brings us one step closer to the answers.

What to expect

We have a variety of studies, some of which take a couple minutes, others that will last up to several years. Some studies can be flexible to your schedule and optimal availability, others need you to come to a scheduled visit within a set number of days.

Whenever we discuss clinical studies with a potential participant, we always want to determine your situation to make your involvement into a positive experience.

Most clinical studies provide some reimbursement for your time. Some clinical studies may help cover travel expenses if coming from a relatively long distance. Clinical trials that involve a treatment will typically provide the required medications, follow-up visits, labs and MRIs as part of the protocol. This may be a consideration if you do not have health care coverage or your deductibles for medications and office visits are high. If you are currently seeing a neurologist/MS specialist that you like, you can continue to see that person while participating in a clinical trial.

Types of clinical research

Investigator-initiated clinical studies are ideas, questions and protocols that are developed by physicians and scientists at the John L. Trotter MS Center. Some study protocol examples might include blood draws, questionnaires, a clinical assessments or MRIs. They can involve a therapy, but most often relay on clinical and laboratory assessments. They can be as short as a couple minutes or may have a number of visits over several months or years.

Industry-sponsored clinical trials are typically performed for regulatory/FDA approval of new therapies. These trials are sponsored by the manufacturer of a treatment seeking either approval for a new indication on the package label. These studies are classified as Phase I, II, III and IV. Clinical trials are most frequently done through an outside coordinating organization that works on behalf of a manufacturer/developer and can involve a dozen to over a hundred sites around the world. Washington University is one of those sites, and we are contracted to enroll participants, provide treatment, perform assessments and collect all the information for regulatory submission. These studies can last anywhere from six months to three years. After enrollment, visits are often quarterly but can vary based upon the protocol. The clinical trial supplies the therapy being studied along with any comparator therapy and covers the costs of the protocol-defined clinical assessments, office visits, labs and MRI scans. Participants are often not aware of which treatment they are receiving (blinded), and we do not get to pick which treatment your will receive (randomized). Sometimes the study will provide you the option for additional visits after the main study with the study treatment supplied to everyone (open-label extension).

Is Restriction of Calories Beneficial During an MS Exacerbation?

A pilot study of adipokines and calorie restriction in Multiple Sclerosis

A pilot study of adipokines and calorie restriction in Multiple Sclerosis

Description

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) mediated by immune and neurodegenerative mechanisms. It is a major cause of disability in young adults. Risk of MS is increased about 2-fold by a high body mass index (BMI). Fat tissue is a source of molecules, collectively known as adipokines that can regulate immune and inflammatory responses.

The purpose of this study is to investigate the effects of a regimen of calorie restriction (achieved by alternate day fasting) in MS patients experiencing a relapse on several blood factors and clinical outcomes.

We will enroll eligible relapsing-remitting MS patients (18-60 years of age)having an MS attack. Enrolled subjects will be randomized (as the flip of a coin) to either:

  1. Every other day calorie restriction (CR) plus intravenous corticosteroid for three days and an oral corticosteroid taper for a week afterwards (10 total days). The steroid treatment is a standard therapy for significant MS relapses; or
  2. the same steroid regimen as above but without the calorie restriction (control group).

At the end of the Acute CR phase, both groups will be offered to enroll in the alternate day fasting regimen for 6 months (Chronic CR phase).

Exclusion criteria

  • BMI less than 23.
  • Chronic disease (excluding MS) that could interfere with interpretation of results.
  • Use of insulin pumps or insulin injections for diabetes.
  • Use of drugs like Warfarin or Coumadin that need to monitor the intake of vegetables containing high levels of vitamin K.
  • Alcoholism, psychiatric problems, life situations that would interfere with study participation and compliance.
  • Patients that are medically required to follow a special diet or food restriction (diabetic, gastric bypass, soft/pureed food, etc.)

Length of trial

Participants will be in the Acute CR phase for 15 days. If participant will decide to be enroll in the Chronic CR phase, the trial will last 6 months.

Publications from the center that report translational work and clinical trials

  1. Avasarala J, Cross AH, Trotter JL: Oligoclonal band number as a marker for prognosis in multiple sclerosis. Archives Neurol. 2001; 58: 2044-2045.
  2. Avasarala JR, Cross AH, Clifford DB, Singer B, Siegel, Abbey EE: Rapid Onset Mitoxantrone-induced Cardiotoxicity in Secondary Progressive Multiple Sclerosis. Multiple Sclerosis 2003; 9:59-62.
  3. Avasarala JR, Cross AH, Trinkaus K: Comparative assessment of Yale Single Question and Beck Depression Inventory Scale in screening for depression in multiple sclerosis. Multiple Sclerosis 2003; 9:307-310.
  4. Attarian HP, Brown KM, Duntley SP, Cross AH: The relationship of sleep disturbances to fatigue in multiple sclerosis. Arch. Neurol. 2004; 61: 535-538.
  5. Naismith RT, Trinkaus K, Cross AH: Phenotype and prognosis in African-Americans with multiple sclerosis: a retrospective chart review. Multiple Sclerosis 2006; 12: 775-781.
  6. Goodman AD, Cohen JA, Cross AH, Rizzo M, Vollmer T, Blight AR: Fampridine-SR in multiple sclerosis: a randomized, double-blind, placebo-controlled, dose-ranging study. Neurology 2008; 1134-41.
  7. Fenoglio C, Scalabrini D, Piccio L, deRiz M, Venturelli E, Cortini F, Villa C, Serpente M, Parks BJ, Rinker J, Bresolin N, Cross AH, Scarpini E, Galimberti D. Candidate gene analysis of selectin gene cluster in patients with multiple sclerosis. J Neurology 2009 256:832-3.
  8. De Jager PL, Jia X, Wang J, de Bakker PI, Ottoboni L, Aggarwal NT, Piccio L, Raychaudhuri S, Tran D, Aubin C, Briskin R, Romano S; International MS Genetics Consortium, Baranzini SE, McCauley JL, Pericak-Vance MA, Haines JL, Gibson RA, Naeglin Y, Uitdehaag B, Matthews PM, Kappos L, Polman C, McArdle WL, Strachan DP, Evans D, Cross AH, Daly MJ, Compston A, Sawcer SJ, Weiner HL, Hauser SL, Hafler DA, Oksenberg JR. Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. Nat. Genet. 2009; 41: 776-82.
  9. Naismith RT, Shepherd BJ, Weihl CC, Tutlam NT, Cross AH. Acute and bilateral blindness due to optic neuropathy associated with copper deficiency. Arch Neurol. 2009; 66: 1025-1027.
  10. Naismith RT, Tutlam N, Xu J, Klawiter EC, Shepherd, JB, Song, SK, Cross AH. Optical Coherence Tomography is Less Sensitive than Visual Evoked Potentials in Optic Neuritis Neurology 2009; 73: 46-52.
  11. Piccio L, Naismith RT, Trinkaus K, Klein RS, Parks BJ, Lyons JA, Cross AH. Changes in B- and T-lymphocyte and chemokine levels with rituximab treatment in multiple sclerosis. Arch Neurol 2010; 67(6):707-714.
  12. Klawiter EC, Benzinger TL, Roy A, Naismith RT, Parks BJ, Cross AH. Spinal cord ring enhancement in multiple sclerosis. Arch Neurol 2010; 67:1395-8. PMCID: PMC3057685
  13. Klawiter EC, Piccio L, Lyons JA, Mikesell R, O’Connor KC,Cross AH. Elevated intrathecal myelin oligodendrocyte glycoprotein antibodies in Multiple Sclerosis. Arch Neurol. 2010; 67: 1102-1108. PMCID: PMC3051403
  14. Qian P,Cross AH, Naismith RT. Lack of response to monoclonal antibody therapy in neuromyelitis optica. Ann Neurol 2011 68: 1207-1209
  15. Naismith RT, Xu J, Tutlam NT, Lancia S, Trinkaus K, Song SK,Cross AH. Diffusion Tensor Imaging in Acute Optic Neuropathies. Predictor of Clinical Outcomes. Arch Neurol 2012; 69: 65-71 doi:10.1001/archneurol.2011.243
  16. Qian P, Lancia S, Alvarez E, Klawiter EC,Cross AH, Naismith RT. Association of neuromyelitis optica with severe and intractable pain. Arch Neurol. 2012; 69:1482-7. PMID:22926050
  17. Alvarez E, Piccio L, Mikesell RJ, Klawiter EC, Parks BJ, Naismith RT, Cross AH. CXCL13 is a Biomarker of Inflammation in Multiple Sclerosis, Neuromyelitis Optica, and Other Neurological Conditions. Mult Scler J 2013 (in press)
  18. Naismith RT, Zu J, Klawiter EC, Lancia S, Tutlam N, Wagner J, Qian P, Trinkaus K, Song SK, Cross AH. Diffusion Tensor Imaging of Spinal Cord Tracts Reveals Disability Substrate in Demyelination. Neurology, 2013 (in press)