Cardiovascular Consequences of NIV Withdrawal in Patients With Myotonic Dystrophy

NCT00745238 | Unknown

• 1 other identifier: 0801
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Myotonic dystrophy lead to highly heterogeneous, multisystemic symptoms including myotonia, progressive muscle weakness, cardiac conduction defects, cataract, metabolic dysfunction, and excessive daytime somnolence. This last symptom is related to respiratory failure and/or to involvement of the central nervous system. However the metabolic disturbances could contribute to it. From the respiratory point of view this disease is characterised by the progressive appearance of respiratory failure of muscular origin but mainly associated with a defect in the central respiratory drive. The treatment for this hypoventilation is non-invasive ventilation (NIV). It is not currently absolutely clear as to the best choice of criteria to judge long term effectiveness of NIV. The most usual criteria are normalisation of daytime blood gases, diminution of respiratory work, improvement in daytime symptoms and improvement in sleep structure. Other criteria are currently little studied, for instance the contribution of the interaction between alveolar hypoventilation and oxygen desaturation during the night and biological deficiencies such as systemic inflammation, glucose intolerance or insulin resistance. Likewise there is little information about the interaction between alveolar hypoventilation and endothelial dysfunction and arterial stiffness both being accurate predictive factors for cardiovascular risks. Aim: to evaluate the impact of NIV on endothelial dysfunction in patients with myotonic dystrophy. The secondary objectives are to assess the impact of NIV on systemic inflammation, arterial stiffness, insulin-resistance, quality of sleep, and daytime vigilance in these patients. Methods: Patients with chronic alveolar hypoventilation already treated by long term NIV will be included. They will have an initial check-up (Visit 1), then will interrupt NIV treatment for four weeks (Visit 2), and then return to NIV treatment. The last check-up will be done four weeks after NIV resumption (Visit3). Expected results: It is expected that NIV withdrawal will results in a deterioration of cardio-vascular parameters (endothelial function and arterial stiffness), metabolic parameters (insulin-resistance and systemic inflammation), quality of sleep and daytime vigilance. Return to NIV treatment may show an improvement of these parameters with a basal state recovery.

Conditions

Myotonia

Keywords

endothelial function; peripheral arterial tone; systemic inflammation; oxidative stress; respiratory and peripheral muscular function

Outcome Measures

Primary Outcomes (1)

• To evaluate endothelial dysfunction (as measured by Peripheral arterial tone (PAT)) and its evolution after four weeks withdrawal of non-invasive ventilation (NIV).

  8 weeks

Secondary Outcomes (1)

• To assess arterial stiffness, systemic inflammation (IL6, TNFα, Leptin, CRP), insulin resistance, DHEA, sleep quality, objective and subjective daytime somnolence and their evolution after four weeks withdrawal of NIV.

  8 weeks

Study Arms (1)

Myotonic Dystrophy 1

EXPERIMENTAL

Other: withdrawal of non-invasive ventilation

Interventions

withdrawal of non-invasive ventilation OTHER

Four weeks withdrawal of non-invasive ventilation

Myotonic Dystrophy 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients (\>18 yrs) suffering from myotonic dystrophy already treated by long term nocturnal non invasive ventilation for more than six months for a chronic hypercapnic respiratory failure (Level of PaCO2 at beginning of the treatment should be between 45 and 55 mmHg)
• Patients should use his (her) non-invasive ventilation more than 4 hours and less than 12 hours per day.
• Patients could have an associated obstructive or/and central sleep apnea.
• NIV treatment should be consider as "efficient ": To allow an improvement of PaCO2 during wakefulness in the morning when using NIV compared to PaCO2 at the beginning of the treatment; To allow an improvement of the nocturnal oxymetry compared to baseline (mean nocturnal SaO2 \> 90%).

You may not qualify if:

• Patients with a concomitant respiratory condition contributing to daytime alveolar hypoventilation.
• Patients judged by investigators as at high cardiovascular risk, this contraindicating NIV withdrawal.
• Patients with cardiac failure and periodic breathing.
• Patients who have had an acute episode of respiratory failure in the previous month.
• Incapacitated patients in accordance with article L 1121-6 of the public health code.
• Patients treated by oral corticosteroids or oral long-term non-steroidal anti-inflammatory drugs (NSAID).

Sponsors & Collaborators

• University Hospital, Grenoble: lead

Study Sites (1)

France.Functional Cardio-Respiratory Exploration Laboratory

Grenoble, Isere, 38000, France

RECRUITING

Related Publications (1)

• 1-Cho DH. Biochim Biophys Acta 2007;1772:195-204. 2-Harper PS. W.B. Saunders ed. London, 1989. 3-Machuca-Tzili L. Muscle Nerve 2005;32:1-18. 4-Lazarus A. J Am Coll Cardiol 2002;40:1645-52. 5-Johansson A. J Intern Med 1999;245:345-51. 6-Johansson A. Int J Obes Relat Metab Disord 2002;26:1386-92. 7-Carter JN. J Clin Endocrinol Metab 1985;60:611-4. 8-Kouki T. Diabet Med 2005;22:346-7. 9-Mammarella. J Neurol Sci 2002;201:59-64. 10-Laberge L. J Sleep Res 2004;13:95-100. 11-Begin P. Am J Respir Crit Care Med 1997;156:133-9. 12-DAngelo MG. Muscle Nerve 2006;34:16-33. 13-Veale D. Eur Respir J 1995;8:815-8. 14-Vgontzas A. Sleep Med Rev 2005;9:211-24. 15-Perrin C. Semin Respir Crit Care Med 2005;26:117-30. 16-Guilleminault C. J Neurol Neurosurg Psychiatry 1998;65:225-32. 17-Mehta S. Am J Respir Crit Care Med 2001;163:540-77. 18-Babu AR. Arch Intern Med 2005;165(4):447-52. 19-Talbot K. Neuromuscul Disord 2003;13(5):357-64.

  BACKGROUND

MeSH Terms

Conditions

Myotonia

Condition Hierarchy (Ancestors)

Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Jean Louis PEPIN, PROFESSOR

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jean Louis PEPIN JP PEPIN, PROFESSOR

CONTACT

00330476765516; JPepin@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2008
• First Posted: September 3, 2008
• Study Start: June 1, 2008
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: August 13, 2012

Record last verified: 2008-09

Locations

FR (1)