Clinical research

New paper published on SMA clinical trial

A paper entitled “Phase II open label study of valproic acid (VPA) in Spinal Muscular Atrophy" was published on May 13 in the online Journal PLoS ONE by Project Cure SMA Group funded by Families of SMA.
The paper presents the data from an open label trial of valproic acid in 42 subjects with SMA to assess safety and explore potential outcome measures to help guide design of future clinical trials.

The results indicated that VPA was well-tolerated and without evident hepatotoxicity. Carnitine depletion was frequent, and temporarily associated with increased weakness in two subjects, indicating a need for co-administration of carnitine with VPA. Clear decline in motor function occurred in several subjects in association with weight gain. Mean fat mass increased without a corresponding increase in lean mass, suggesting that weight gain is likely to be significant confounding factor in future VPA clinical trials. A significant improvement in motor function, as measured by the Modified Hammersmith Functional Motor Scale (MHFMS), was observed in participants younger than 5 years of age.

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New clinical trial on adult SMA III patients

It’s ongoing the start of a clinical trial to assess the tolerability and efficacy of salbutamol in adult patients with SMA 3.
This two-years long, randomized, double-blind, placebo-salbutamol trial takes place in collaboration with several centers of excellence of Italy: the Center for Genetics at the Catholic University of Rome (Dr. Brahe), the Policlinico Gemelli in Rome (Dr. Mercuri), the Neurological Clinic of Turin Molinette (Dr. Mongini), the Neurological Clinic of University of Padova (Prof. Angelini), the Besta Institute in Milan, the Neurological Clinic of Policlinico of Messina (Prof. Vita), the Center of Cardiomiology of the University of Naples (Dr. Politano).

Sixty patients with genetic diagnosis of SMA 3, aged between 18 and 50 years, will be enrolled in the study. Women who are pregnant or breastfeeding will not be included in the study.
The study includes a visit for selection with a complete clinical check-up in which blood tests will be performed, samples for molecular analysis, cardiologic evaluation, evaluation of bone mass, evaluation of muscle strength and spirometry tests. Patients with all the required criteria for inclusion will be enrolled and randomized to drug or placebo group. A tour of inspection will be performed after 1, 3, 6 and 12 months from the date of commencement.
The purpose of this study is to verify whether the administration of salbutamol increases the SMN2 transcripts with a corresponding improvement in the clinical picture of the patient. The study was approved by the Ethic Committees of participating institutions and was funded by the Italian Drug Agency (AIFA).

For more information and/or to offer the availability, please call 02-23942255 or 3383034731, or send an email to This e-mail address is being protected from spambots. You need JavaScript enabled to view it

(source: Famiglie SMA)

Trophos trial update

Here is a first update, reported by the French news Myoline (May-June 2008)..

It's ongoing the recruitment of additional 10 SMA patients for participation in clinical trial aimed at assessing the clinical tolerance and pharmacokinetics of TRO19622, administered orally in a single dose and in repeated doses. This phase Ib trial, conducted in the open (all patients receiving treatment), takes place at four clinical centers of France: Raymond Poincaré Hospital in Garches (Prof. Estournet, principal investigator), the University Center of Marseille (Prof. Chabrol), Lille (Dr Cuisset) and Toulouse Hospital (Dr Cances).

The inclusion of patients was carried out according to specific criteria: they have a SMA Type Ib, II or III, no matter how long (but with onset of the disease before the age of 15) with genetically confirmed diagnosis, aged between 6 and 25 years. After a visit for selection and a complete clinical check-up (motor function tests, tests of functional autonomy, ECG, breathing tests, chest X-rays, blood tests), patients with all the required criteria are invited and admitted to hospital for a period of 48 hours. The TRO19622 is administered in a single dose of 125 mg orally and are valued parameters of tolerance and pharmacokinetics. In the fifth and tenth day blood samples are done at home to detect the dose of TRO19622. An outpatient visit (in 15th day) precede the second study period from 16th to 25th day. During this period 125 mg daily of TRO19622 are administered. A second hospitalization of 24 hours held in 25th day, for repeated blood samples for the detection of the assay of TRO19622. The 27th and 29th days additional blood samples at home. During the study ECG monitoring is made in the days 10, 17, 19, 27 and 29 by a specialist cardiologist. The visit at the end of treatment takes place on day 34 and includes a complete clinical check-up. A final tour of inspection is performed after 65 days from the date of commencement.

This trial began in 2007 and the last patients was included on july 2008. Depending on the results, the development of TRO19622 will continue with further clinical trials for evaluation of tolerance and efficacy in patients SMA.

Last update: success of the trial, continuing the rush towards the drug!
Read the news.

Trial Carnival results

After three years of hard work, Families of SMA is pleased to have the first results from the Phase 2 CARNI-VAL trial conducted by Project Cure SMA to test the safety and possible efficacy of valproic acid (VPA) and carnitine in children with SMA. This study involved the work of more than 30 professionals at 6 different clinical testing sites. 94 children and their families enrolled in the trial and participated inmore than 450 site visits. Over a half million pieces of data are being analyzed. In this letter, I am going to briefly summarize the first results from the Phase 2 trial and then discuss the implications for the new Type I trial.

The results
This issue of Compass includes a detailed report on the Phase 2 trial results for one sample group comprised of children with SMA Type II, ages 2-8 years. They were randomly given either the drug treatment of VPA and carnitine or a placebo for the first six months of the trial. Every child then received drug treatment for the second six month period.
Overall, children who received the drug when compared to placebo over a six-month period showed no significant improvement in motor function as measured by the Modified Hammersmith Functional Motor Scale (MHFMS), the primary outcome we used for the study. A subgroup analysis on younger and lighter children, aged 2-3 years of age who received a full year of drug treatment, demonstrated a significant probability of increased motor function when compared to the placebo group. These results, like those from the open-label VPA study, suggest that responder and non-responder SMA patient populations to this drug may exist. Weight gain and age appear be significant factors in responding to the drug. Such a hypothesis would require additional formal testing to prove. In addition, the CARNI-VAL data indicate that increased fat mass is negatively related to an increase in motor function, suggesting that weight needs to be carefully monitored when administering this drug. At this point in the data analysis, drug-related weight gain is the main adverse effect in this population of children.

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