Background

Lifestyle changes have been demonstrated to impact pathophysiology in Multiple Sclerosis (MS). Various diet and exercise protocols have been reported to improve symptoms and function in persons with MS. Evidence is accumulating that interventions as early as possible in the disease course are warranted. The objective of this study was to investigate the effect of a remotely delivered lifestyle program focusing on specific diet and exercise recommendations in persons with early MS.

Methods

MS patients, with disease diagnosis no more than 2 years prior, were recruited from the patient population of the MS clinic of the Pacific Neuroscience Institute. Participants followed recommendations for diet and exercise delivered via remote heath coaching. Each participant received 6 sessions with a health coach over a 12-week period. They were given parameters of a Mediterranean-type diet to follow, and specific and individualized recommendations about duration, intensity and type of exercise and physical activity. Outcome measures included Quality of Life (QOL), cognition (Symbol Digit Modalities Test, SDMT), fatigue (Multiple Sclerosis Fatigue Impact Scale, MFIS), fitness (estimated with Metabolic equivalents, METS) and other objective and patient reported outcomes (PRO). Changes in outcomes were analyzed using mixed effects general linear models and standardized pre-post differences.(Cohen's d) RESULTS: Fifteen persons with early (≤ 2 years) MS enrolled in the study, 14 of whom completed the study. We observed significant improvements in QOL (p = 0.02), SDMT (p = 0.006), fatigue(p = 0.005), fitness (p = 0.04), and other PRO and objective metrics at the end of the protocol compared to baseline. Adherence and patient satisfaction measures were high.

Conclusions

Specific and individualized lifestyle recommendations can be effectively delivered remotely, and may produce improvement in symptoms and function in persons with early MS. Larger controlled trials of these interventions are warranted.

Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. While current medication reduces relapses and inflammatory activity, it has only a modest effect on long-term disability and gray matter atrophy. Here, we have characterized the potential neuroprotective effects of testosterone on cerebral gray matter in a pilot clinical trial. Ten men with relapsing-remitting MS were included in this open-label phase II trial. Subjects were observed without treatment for 6 months, followed by testosterone treatment for another 12 months. Focal gray matter loss as a marker for neurodegeneration was assessed using voxel-based morphometry. During the non-treatment phase, significant voxel-wise gray matter decreases were widespread (p≤ 0.05 corrected). However, during testosterone treatment, gray matter loss was no longer evident. In fact, a significant gray matter increase in the right frontal cortex was observed (p≤ 0.05 corrected). These observations support the potential of testosterone treatment to stall (and perhaps even reverse) neurodegeneration associated with MS. Furthermore, they warrant the investigation of testosterone's neuroprotective effects in larger, placebo controlled MS trials as well as in other neurodegenerative diseases. This is the first report of gray matter increase as the result of treatment in MS.

Background

There are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.

Methods

We enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis.

Results

Of 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.

Conclusions

In a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).