Evaluate the Effort Test as a Therapeutic Monitoring Tool in Acute Rhabdomyolyses

Summary

The prognosis of rhabdomyolyses related to hereditary diseases of metabolism is poor and treatments are only symptomatic. Rhabdomyolysis outbreaks are frequently precipitated by fever and fasting. They are unpredictable. In spite of the care of patient in an intensive care unit, the occurrence of renal failure and heart rhythm disorders explains a significant acute-phase mortality rate. There is an urgent need to understand the pathophysiological mechanisms of rhabdomyolyses related to hereditary diseases of metabolism, in order to identify specific treatments.

Patients with rhabdomyolyses have few clinical signs outside of access. So there is a methodological difficulty in following a treatment test. There is an urgency to identify follow-up parameters in anticipation of new therapies.

The objective of this study is to validate the hypothesis that effort test and cardiac function parameters are usable in the treatment monitoring for patients with acute rhabdomyolysis linked to a hereditary disease of metabolism and thus propose the effort test as an assessment tool for future clinical trials. In order to do so, the correlation between the results of the effort tests, performed to each patient with rhabdomyolysis related to a hereditary disease of metabolism, with the severity of the disease will be evaluated. This study is original because it opens up innovative prospects for monitoring in the field of hereditary diseases of metabolism, with the identification of new monitoring tools.

Conditions

• Rhabdomyolysis Linked to a Hereditary Disease of Metabolism

Interventions

OTHER

Effort test

Cardiac function: Echocardiography: left ventricular ejection fraction and global longitudinal strain will be measured. Cardiopulmonary exercise test (CPET): left ventricular stroke volume was assessed noninvasively using a thoracic bioelectrical impedance device : maximal stroke volume at the peak of effort will be considered. Peripheral muscle function: * CPET: Oxygen uptake (VO2) (and carbon dioxide) output are measured. The slope of the relationship (dQ/dVO2) will be calculated between cardiac output (Q) and VO2 using measurements of Q (using measure of the stroke volume by thoracic bioelectrical impedance device) and VO2 at rest as well as during submaximal and maximal exercise * Muscle oxygenation is measured using a near-infrared spectroscopy device. * VO2 et Q will be measured : dQ/dVO2 is high in case of oxydation defect; If Q is low because of a concommittant cardiac impairement, the DAV = VO2/Q, and DO = (Q x DAV) / (200 - DAV) will be calculated.

OTHER

Functional tests on fibroblasts

Functional tests performed on fibroblasts in primary culture, using as tracers of stable isotope-labeled substrates. The metabolites of interest are assayed in mass spectrometry.

Sponsors & Collaborators

• URC-CIC Paris Descartes Necker Cochin

  collaborator OTHER

• Assistance Publique - Hôpitaux de Paris

  lead OTHER

Principal Investigators

• Pascale de Lonlay · Assistance Publique - Hôpitaux de Paris

• Antoine Legendre, MD, PhD · Assistance Publique - Hôpitaux de Paris

• Florence Habarou, MD, PhD · Assistance Publique - Hôpitaux de Paris

• Caroline Tuchmann-Durand, Pharm. D, PhD · Assistance Publique - Hôpitaux de Paris

Eligibility

Min Age

6 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-25

Primary Completion

2021-12-31

Completion

2021-12-31

Countries

• France

Study Locations