Clinical Trials and Studies Fall 2009

Article Highlights:

The latest on clinical trials as of September 2009.

by Quest Staff on October 1, 2009 - 1:53pm

QUEST Vol. 16, No. 4

The following article contains items about: Friedreich's ataxia, Charcot-Marie-Tooth disease, myotonic muscular dystrophy type 1, amyotrophic lateral sclerosis, Emery-Dreifuss muscular dystrophy and distal muscular dystrophy (Miyoshi myopathy)

Idebenone not effective in 70 children with FA

On May 19, 2009, Santhera Pharmaceuticals ( reported that a phase 3 trial of its idebenone compound Catena showed the drug was not associated with a statistically significant benefit in 70 children between 8 and 17 years old with Friedreich’s ataxia (FA) who took it for six months. The drug appeared safe and well tolerated at doses up to 2,250 milligrams per day.

Santhera’s press release says there’s an ongoing phase 3 trial of Catena now being conducted in Europe that has a different design from the U.S. study and for which results are expected in 2010.

Friedreich’s ataxia typically begins in childhood or adolescence, causing weakness, loss of coordination and heart problems.

The European trial is a year long, and includes 232 participants, predominantly adults. Santhera says if the results of this European trial are positive, they will form the basis of filings for regulatory approval in the United States and Europe.

Idebenone is believed to improve energy production in cellular structures called mitochondria. Earlier studies showed the drug was safe and well tolerated in Friedreich’s ataxia and that there was a statistical trend toward dose-related improvement in neurological function associated with its use.

Santhera’s press release quotes Sue Perlman, clinical professor of neurology at the University of California-Los Angeles and one of the two study investigators on the U.S. trial, as saying, “I still strongly support the disease-modifying effect of Catena in Friedreich’s ataxia. I believe it slows the progression of the neurological and cardiac aspects of this condition over time.”

She strongly recommended that patients continue to take the drug in the open-label extension study so that the investigators can gather as much longer-term data as possible.

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Jury still out on vitamin C for CMT1A

A recent trial has shown inconclusive results from various doses of vitamin C (ascorbic acid) in patients with the peripheral nerve disease type 1A Charcot-Marie-Tooth disease (CMT1A), and the jury remains out on this form of treatment, says Michael Shy, an MDA grantee at Wayne State University in Detroit.

Shy, a neurologist, is conducting a trial of high-dose vitamin C in CMT with neurologist Richard Lewis, also an MDA grantee at Wayne State. That trial is now closed, and results are under analysis.

According to results published in the June 2009 issue of Lancet Neurology, a one-year trial of high-dose vitamin C in 81 children ages 2 to 16 with CMT1A in Australia showed the treatment was safe and well tolerated but not effective.

However, some of the mildly affected patients in that trial appeared to perform better on relatively low doses of vitamin C than children taking a placebo. (Their story was highlighted on Australian television on May 28, 2009. See the Webcast at For most patients, the results were neutral.

Shy expressed concerns about the design of the study in a commentary in the same issue of Lancet Neurology in which the results were reported.

Shy says the Australian study was conducted in growing children, which makes the analysis particularly difficult to interpret. (The MDA-supported study includes adolescents and adults ages 13 to 70.)

“Kids grow, and they grow at different rates at different ages,” he says. “There’s this whole field of how to evaluate children with neuromuscular disease that’s evolving. We’re in the process of creating ways of evaluating children with CMT, through a study that’s in part funded by another MDA grant. One of the aims is to develop a CMT pediatric scoring system.”

He says the outcome measure the Australian researchers used was based on an electrodiagnostic measurement called nerve conduction velocity (the speed at which nerve impulses travel), values for which have been shown not to correlate with impairment in movement or sensation in children with CMT.

The Australian study used varying doses of vitamin C in the children, but they “never got to a high dose.”

“Kids are an important group,” says Shy, “but they need to be studied in a more complete and carefully designed manner.”

Other studies now under way, Shy says, may show there isn’t much effect of 1 gram of vitamin C per day on CMT. However, he says, most of these studies are limited by small numbers of participants and short durations.

Shy and Lewis note that results of a French study, presented at a meeting in Antwerp, Belgium, in July 2009, suggest that a trial of 3 grams of vitamin C per day in people with CMT is “looking positive” but that this trial also may not have been designed to yield a definitive answer.

“The bottom line is that the definitive study is going to be the MDA-supported CMT1A study,” Shy says, noting that he and Lewis agree. “It’s 4 grams a day, which is a high dose, and is powered [has enough participants and lasts long enough] to give a meaningful result.

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Iplex shows limited benefit in MMD1; development on hold

The drug Iplex, developed by the Richmond, Va., biopharmaceutical company Insmed (, did not improve muscle function, strength or endurance in a phase 2 trial in type 1 myotonic dystrophy (MMD1, or DM1), the company announced June 25, 2009.

No conclusions were reached about the effect of Iplex on cognitive function, gastrointestinal function or pain, because of a limited number of trial participants with problems in these areas.

However, measurements of insulin sensitivity — the ability of cells to respond to insulin — did show improvements in trial participants. Insulin sensitivity was assessed by serum levels of glucose and insulin, as well as cholesterol and triglycerides.

MDA helped support the clinical trial, which involved 69 adults with MMD1 who were randomly assigned to receive either Iplex or a placebo for six months. Neither participants nor investigators knew who received the drug until after all data had been collected.

On July 27, Insmed announced it would analyze the available data on Iplex for MMD1 and the limited data available related to the drug’s usage in amyotrophic lateral sclerosis (ALS) before deciding whether to proceed with development of this compound for either disease.

Iplex is a combination of a protein called insulin-like growth factor 1 (IGF1) and IGF binding protein 3. It was approved in the United States in 2005 for treatment of children with growth failure due to severe deficiency of IGF1. (Insmed no longer markets Iplex for this purpose in the United States after losing a patent dispute.)

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People with LGMD2B, Miyoshi myopathy sought for patient registry

The Jain Foundation, dedicated to research in diseases that result from a deficiency of the muscle protein dysferlin, is seeking people with type 2B limb-girdle muscular dystrophy (LGMD2B) or a distal muscular dystrophy called Miyoshi myopathy for its database (registry) of patient-submitted information.

LGMD2B and Miyoshi myopathy are caused by mutations in the dysferlin gene that lead to a deficiency of the dysferlin protein. A free mutation analysis (DNA diagnosis) is offered to registrants who meet the necessary criteria.

For more information, go to and click on Patient Registration; or contact Esther Hwang at (425) 882-1440 or

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