Investigating low protein diet as a treatment for Bethlem myopathy and Ullrich congenital muscular dystrophy

Start Date
01/10/2011
Expected end Date
01/12/2013
Location
Europe
Status
Active but not recruiting

What is the aim of the trial?

This pilot study will test the safety and effect of a low protein diet on certain cellular processes in the body that may have a role in causing symptoms of Bethlem myopathy and Ullrich congenital muscular dystrophy.

Bethlem myopathy and Ullrich congenital muscular dystrophy are caused by a fault in any one of the three genes responsible for the production of the protein collagen VI. This causes a deficiency of collagen VI protein. Collagen VI is located on the outside of the cell as part of a complex mixture of other proteins and sugars; this is called the extracellular matrix or ECM. The extracellular matrix provides structural support to the cell as well as performing various other important functions such as sticking cells together and mediating communication between cells.

Previously researchers have also found some evidence that cells from patients with either Bethlem myopathy or Ullrich congenital muscular dystrophy grown in the laboratory have dysfunctional ‘mitochondria’. Mitochondria are the batteries of cells, providing them with energy. Each cell has hundreds of mitochondria. It is thought that the cells from these patients are also not very good at removing the dysfunctional mitochondria, which leads to more muscle cells dying. A recent study in mice showed that changing the diet of the mice could improve the ability of muscle cells to remove dysfunctional mitochondria resulting in healthier looking muscles under the microscope. This study aims to gather the first evidence as to whether the same could be achieved in patients with Bethlem myopathy or Ullrich congenital muscular dystrophy.

Who can be involved in the trial?

This trial will enroll eight patients with Bethlem myopathy or Ullrich congenital muscular dystrophy by invitation only. They must 18 years or older and both men and women will be invited to take part. Women must have a negative pregnancy test, not be breastfeeding and use contraception during the study. Some liver or kidney diseases may make patients ineligible for the study.

What happens during the trial?

The trial starts with a three month observational phase followed by 12 months of a low protein diet. During this 12 month phase patients will receive a diet of 0.6-0.8 grams of protein per kilogram of body weight per day. The diet will include a normal amount of calories per day.

A muscle biopsy will be taken just before starting the low protein diet and after completing the 12 month diet plan. The researchers will look for a certain protein in the muscle biopsy that indicates whether the cells are efficiently removing damaged mitochondria from the cells. Blood samples will also be taken and analysed to find out if less invasive blood tests could replace the need for muscle biopsies in similar studies in the future. The size and strength of the participant’s muscles will also be assessed.

Where is the study taking place?

This study will be taking place in:
Bologna, Italy

In most circumstances, for somebody to participate in a clinical trial, they need to live near the team of people who are conducting the research, because they need to be closely monitored.

How could the results of the trial benefit patients?

This is a small pilot study to find out if a low protein diet is a feasible approach to attempt to ease some of the symptoms of Ullrich congenital muscular dystrophy and Bethlem myopathy. If this study shows that there are indications that this approach has potential, it will lead on to a larger trial which includes a control group of patients who do not follow the low protein diet. This will allow more accurate measurement of the effectiveness of the diet.

Contact Details:

Luciano Merlini, MD

Email: merlini@ior.it

Who is funding this study?

  • Instituto Ortopedico Rizzoli

Official name of the Trial:

Low Protein Diet to correct defective autophagy in Patients with Collagen VI Related Myopathies

Trial study number:

NCT01438778

Further trial details:

For further information on the trial and detailed inclusion and exclusion please click on the link below. Sometimes these details can be quite technical. If you have any questions please discuss this with your clinician or contact the clinical trial organisers.

www.clinicaltrials.gov/show/NCT01438788

Background information and related links:

This pilot study will test the safety and effect of a low protein diet on certain cellular processes in the body that may have a role in causing symptoms of Bethlem myopathy and Ullrich congenital muscular dystrophy.

Bethlem myopathy and Ullrich congenital muscular dystrophy are caused by a fault in any one of the three genes responsible for the production of the protein collagen VI. This causes a deficiency of collagen VI protein. Collagen VI is located on the outside of the cell as part of a complex mixture of other proteins and sugars; this is called the extracellular matrix or ECM. The extracellular matrix provides structural support to the cell as well as performing various other important functions such as sticking cells together and mediating communication between cells.

Previously researchers have also found some evidence that cells from patients with either Bethlem myopathy or Ullrich congenital muscular dystrophy grown in the laboratory have dysfunctional ‘mitochondria’. Mitochondria are the batteries of cells, providing them with energy. Each cell has hundreds of mitochondria. It is thought that the cells from these patients are also not very good at removing the dysfunctional mitochondria, which leads to more muscle cells dying. A recent study in mice showed that changing the diet of the mice could improve the ability of muscle cells to remove dysfunctional mitochondria resulting in healthier looking muscles under the microscope. This study aims to gather the first evidence as to whether the same could be achieved in patients with Bethlem myopathy or Ullrich congenital muscular dystrophy.

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