Ice water test in multiple sclerosis: A pilot trial

The serine proteinase tissue-type plasminogen activator (t-PA) and the metalloproteinase gelatinase B (MMP-9) have recently been demonstrated in MS lesions. Both enzymes are interconnected in an enzyme cascade which contributes to destruction of the blood brain barrier and demyelination and both enzymes are inhibited by D-penicillamine. Metacycline was shown in in vitro experiments to inhibit gelatinase B. The combination of peroral D-penicillamine plus metacycline was evaluated in a double-blind placebo-controlled way in two groups of 10 patients suffering from secondary progressive multiple sclerosis. The major objectives of this pilot trial were to examine the safety of this combination and the possibility of blinding, while the effect on disease progression was considered as a secondary endpoint. Over a follow-up period of 1 year and in this selected patient group, there was no significant improvement in the Expanded Disability Status Scale score (EDSS) as compared with that of the placebo-control group. Toxicity was too high to consider additional trials with this combination of metalloproteinase inhibitors. Although peroral treatment is by most MS patients acknowledged as a major improvement in treatment compliance, one has to await the development of more selective and efficaceous protease inhibitors than those used in the combination therapy described here.

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Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458517703802 ◽

2017 ◽

Vol 24 (4) ◽

pp. 501-511 ◽

Cited By ~ 32

Author(s):

Jeffrey A Cohen ◽

Peter B Imrey ◽

Sarah M Planchon ◽

Robert A Bermel ◽

Elizabeth Fisher ◽

...

Keyword(s):

Multiple Sclerosis ◽

Scale Score ◽

Pilot Trial ◽

Progressive Multiple Sclerosis ◽

Expanded Disability Status Scale ◽

Serious Adverse Events ◽

Mesenchymal Stem Cell Transplantation ◽

Disability Status ◽

Magnetic Resonance Imaging Mri

Background: Mesenchymal stem cells (MSCs) exhibit immunomodulatory, tissue-protective, and repair-promoting properties in vitro and in animals. Clinical trials in several human conditions support the safety and efficacy of MSC transplantation. Published experience in multiple sclerosis (MS) is modest. Objective: To assess feasibility, safety, and tolerability and explore efficacy of autologous MSC transplantation in MS. Methods: Participants with relapsing-remitting multiple sclerosis (RRMS) or secondary progressive multiple sclerosis (SPMS), Expanded Disability Status Scale score 3.0–6.5, disease activity or progression in the prior 2 years, and optic nerve involvement were enrolled. Bone-marrow-derived MSCs were culture-expanded and then cryopreserved. After confirming fulfillment of release criteria, 1–2 × 106 MSCs/kg were thawed and administered IV. Results: In all, 24 of 26 screened patients were infused: 16 women and 8 men, 10 RRMS and 14 SPMS, mean age 46.5, mean Expanded Disability Status Scale score 5.2, 25% with gadolinium-enhancing magnetic resonance imaging (MRI) lesions. Mean cell dosage (requiring 1–3 passages) was 1.9 × 106 MSCs/kg (range, 1.5–2.0) with post-thaw viability uniformly ⩾95%. Cell infusion was tolerated well without treatment-related severe or serious adverse events, or evidence of disease activation. Conclusion: Autologous MSC transplantation in MS appears feasible, safe, and well tolerated. Future trials to assess efficacy more definitively are warranted.

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High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial

Multiple Sclerosis Journal - Experimental Translational and Clinical ◽

10.1177/2055217320903474 ◽

2020 ◽

Vol 6 (1) ◽

pp. 205521732090347 ◽

Cited By ~ 5

Author(s):

Jan Dörr ◽

Priscilla Bäcker-Koduah ◽

Klaus-Dieter Wernecke ◽

Elke Becker ◽

Frank Hoffmann ◽

...

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Disease Activity ◽

Sample Size ◽

Pilot Trial ◽

Vitamin D Supplementation ◽

High Dose ◽

Clinical Relapse ◽

Lesion Development ◽

Cholecalciferol Supplementation

Background Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity. Objectives The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing–remitting MS or clinically isolated syndrome. Methods The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-β1b. Results Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disability progression) and radiographical (T2-weighted lesion development, contrast-enhancing lesion development, brain atrophy) did not differ between both treatment arms. Post-study power calculations suggested that the sample size was too low to prove the hypothesis. Conclusions The results neither support nor disprove a therapeutic benefit of high-dose VD supplementation but provide a basis for sound sample size estimations in future confirmatory studies. www.clinicaltrials.gov/NCT01440062

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The Value of the Ice Water Test in the Management of the Neurogenic Bladder

American Journal of Physical Medicine & Rehabilitation ◽

10.1097/00002060-198810000-00008 ◽

1988 ◽

Vol 67 (5) ◽

pp. 225-227 ◽

Cited By ~ 5

Author(s):

Mario T. Balmaseda ◽

H Thomas Reynolds ◽

Chrisanne Gordon

Keyword(s):

Neurogenic Bladder ◽

Water Test ◽

Ice Water

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