Myotonia Clinical Trial
Official title:
Four Weeks Withdrawal of Non-invasive Ventilation (NIV) in Patients With Myotonic Dystrophy: Cardiovascular, Metabolic and Daytime Vigilance Induced Changes
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.
Status | Recruiting |
Enrollment | 35 |
Est. completion date | December 2012 |
Est. primary completion date | December 2012 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
INCLUSION CRITERIA: - 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%). EXCLUSION CRITERIA: - 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). |
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Supportive Care
Country | Name | City | State |
---|---|---|---|
France | France.Functional Cardio-Respiratory Exploration Laboratory | Grenoble. | Isere |
Lead Sponsor | Collaborator |
---|---|
University Hospital, Grenoble |
France,
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.
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Yes | |
Secondary | To assess arterial stiffness, systemic inflammation (IL6, TNFa, Leptin, CRP), insulin resistance, DHEA, sleep quality, objective and subjective daytime somnolence and their evolution after four weeks withdrawal of NIV. | 8 weeks | Yes |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT06411288 -
Global Study of Del-desiran for the Treatment of DM1
|
Phase 3 | |
Completed |
NCT00832000 -
Effectiveness of Mexiletine for Treating People With Non-Dystrophic Myotonia
|
Phase 2 |