Clinical Trials July-August 2008

Article Highlights:

The latest on active clinical trials as of June 2008

by Quest Staff on July 1, 2008 - 10:50am

QUEST Vol. 15, No. 4

This article contains items about: Duchenne muscular dystrophy, Becker muscular dystrophy, Lambert-Eaton myasthenic syndrome, myasthenia gravis, Charcot-Marie-Tooth disease 1A, spinal muscular atrophy type 1, amyotrophic lateral sclerosis (ALS)

For details about clinical trials and studies and disease registries, visit Clinical Trials and use the search boxes.

Several of the following announcements, designated AAN, are from the 60th annual meeting of the American Academy of Neurology, held in April in Chicago (2008).

Compressed prednisone schedule in DMD may reduce some side effects

Two days a week of the corticosteroid prednisone at a high dose appears to be almost as beneficial as a daily moderate dose of the drug in boys with Duchenne muscular dystrophy (DMD), and some side effects may be less severe, investigators reported.

The yearlong, multicenter study, supported by MDA and the National Institutes of Health, was conducted by Diana Escolar at Children’s National Medical Center in Washington, with colleagues at many institutions.

The investigators analyzed data from 64 boys with DMD who were 4 to 10 years old, had not previously taken corticosteroids, and were still walking.

The boys were randomly assigned to take prednisone at 0.75 milligrams per kilogram every day, or to take prednisone at 10 milligrams per kilogram per day two days a week. Neither the boys nor the investigators knew who was on which schedule. (Boys on the two-day prednisone schedule received “dummy” pills on the no-prednisone days.)

Effects on strength maintenance were similar in the two groups, but time required to get up from the floor was better in the daily prednisone group.

Growth retardation, a known prednisone side effect, was less severe in the two-day, high-dose prednisone group, but weight gain, another serious side effect, was the same in both groups after a year. AAN

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Pentoxifylline benefits minimal in DMD

Two studies of the drug pentoxifylline in Duchenne muscular dystrohy (DMD) have yielded somewhat disappointing results, investigators reported. It had been hoped that pentoxifylline might slow disease progression by increasing blood flow, reducing scar tissue formation and countering inflammation.

A multicenter study in the United States conducted by Diana Escolar at Children’s National Medical Center in Washington, with many others at different clinics, tested pentoxifylline for a year in 17 boys with DMD who were between 4 and 9 years old and who hadn’t taken corticosteroids (like prednisone). Of 17 patients initially enrolled, only nine completed the study. Strength measurements didn’t show a significant change during the study. Five of the eight participants who withdrew did so because of intolerable side effects, such as nausea and vomiting and reduction of white blood cell numbers.

The investigators said the lack of deterioration in strength in a year’s time suggests a possible beneficial effect on disease progression and warrants further study with a different formulation of pentoxifylline. AAN

A separate DMD study conducted at centers in the United States, Italy, Canada, Israel, Australia and Argentina tested the effect of pentoxifylline plus prednisone.

Diana Escolar and many others tested this drug combination against prednisone plus a placebo in 64 boys with DMD, 57 of whom completed the study. The average age was 10.

Strength measurements at one year were not significantly different between the two groups, but the pentoxifylline-treated patients had more coagulation abnormalities, skin problems and gastrointestinal side effects.

The investigators concluded that pentoxifylline was well tolerated in this group but had no effect in slowing DMD disease progression compared to prednisone alone. AAN

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Dystrophin mutation analysis predicted age of onset of cardiac problems in BMD

Investigators reported the age of onset of cardiac problems in boys with Becker muscular dystrophy (BMD) can be approximately predicted from the location and type of mutation in the gene for the muscle protein dystrophin.

They say their analysis of 126 BMD patients identified dystrophin mutations that predispose boys to cardiac muscle deterioration (cardiomyopathy). The team included John Kissel and Jerry Mendell, codirectors of the MDA clinic at Nationwide Children’s Hospital in Columbus, Ohio. AAN

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Boys with DMD or BMD responded to ACE inhibitor treatment of heart problems

A research group that included Jerry Mendell and John Kissel, co-directors of the MDA clinic at Nationwide Children’s Hospital in Columbus, Ohio, found treatment with angiotensin converting enzyme (ACE) inhibitors reversed heart-muscle dysfunction in 12 of 19 boys with DMD or BMD, had no effect on four, and didn’t have a sustained effect in three. The investigators said more data are required before they can make definitive recommendations about ACE inhibitors in these diseases and that cardiac magnetic resonance images (MRIs) might be better than echocardiograms in assessing DMD- and BMD-related heart dysfunction. AAN

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Antibodies to SOX1 protein may indicate lung cancer in LEMS

The presence of immune-system proteins (antibodies) formed against a cell protein called SOX1 is correlated with the presence of lung cancer in patients with Lambert-Eaton myasthenic syndrome (LEMS), according to a multinational study.

LEMS, which involves debilitating weakness, results from a mistaken immune-system attack on calcium channels on the ends of nerve fibers. These calcium channels are needed for transmission of chemical signals from nerve to muscle fibers, and immune-system antibodies destroy them.

Doctors have long known that people with LEMS also have lung cancer about 40 percent to 60 percent of the time, and it’s known that the inadvertent attack on nerve-fiber calcium channels is an unfortunate “side effect” of the immune system’s attack on similar calcium channels on the surface of lung-cancer cells.

Now, Francesc Graus at the University of Barcelona (Spain) and colleagues, who published their findings March 18 in Neurology, have identified SOX1, a protein found inside lung-cancer tumor cells, as another target of the immune system as it tries to fight the tumor. (Antibodies against SOX1 don’t affect the nerve or muscle fibers.)

When Graus and colleagues studied 55 people with LEMS and a type of lung cancer called small-cell lung carcinoma, and 50 with LEMS alone, they found SOX1 antibodies in the blood of 35 (64 percent) of those with both conditions and in none of those with LEMS alone.

The investigators conclude that detection of SOX1 antibodies may become a useful tool in early detection of lung cancer in patients with LEMS.

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Four small studies found rituximab may help in treatment-resistant MG

Four research groups reported improvement of treatment-resistant myasthenia gravis (MG) with the drug rituximab.

A group based in Barcelona, Spain, reported a dramatic improvement with rituximab in six patients with MG who had not responded to other medications. AAN.

When a group that included Rup Tandan, director of the MDA clinic at the Fletcher Allen Health Care Center in Burlington, Vt., tested rituximab in six female patients, all of whom had not responded well to other treatments, they found a trend toward improvement in muscle strength scores after rituximab treatment and “significant and continuous” improvement in scores on a scale measuring activities of daily living. AAN

A group that included Alan Pestronk, MDA clinic director at Washington University in St. Louis, reported using rituximab to successfully treat two patients with MG who had not responded to other forms of therapy. AAN

A French research team reported following five patients with MG who had not responded to other treatments. After two years of treatment with rituximab, all patients had stopped corticosteroid medications and reduced their dose of cholinesterase inhibitor medications (two common treatments for MG). AAN

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CMT1A may worsen with passage from parent to child

An Israeli group reported that type 1A Charcot-Marie-Tooth disease (CMT1A), which results from a mutation on chromosome 17 that causes an excess of the PMP22 protein, appears to worsen as it’s passed from parent to child. In 21 out of 23 parent-child pairs, and in 14 out of 16 families studied, there was an earlier age of symptom onset in the children than in their parents, and the average severity in the younger generation was slightly higher than in the parental generation. The researchers said they don’t know what the underlying mechanism of this phenomenon might be. AAN

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Valproic acid and carnitine to be tested in SMA1

A trial of valproic acid and carnitine in 36 infants with type 1 spinal muscular atrophy (SMA1) who are 2 weeks to 9 months old opened in April at the University of Utah in Salt Lake City, with additional sites in Baltimore; Detroit; Columbus, Ohio; Madison, Wisc.; Montreal; and Cologne, Germany. Valproic acid may increase production of the needed SMN protein in children with SMA, and carnitine has been added because valproic acid depletes it in the body. The study will last about a year. See; or contact Sandra Reyna at (801) 581-3551 or

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MDA supports 1st U.S. trial of lithium in ALS

An MDA-supported clinical trial of lithium carbonate, a medication commonly used to treat bipolar disorder, is set to begin in people with ALS following reports the drug may dramatically slow the progress of this disease. The study will involve 10 sites throughout the United States. Principal investigator is neurologist Robert Miller, director of the Forbes Norris MDA/ALS Research Center at California Pacific Medical Center in San Francisco.

The study is an effort to confirm or refute the findings of a recent Italian trial of lithium carbonate in ALS conducted at the University of Pisa and other institutions. For more information:

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