MyotoniaNCT00745238
Cardiovascular Consequences of NIV Withdrawal in Patients With Myotonic Dystrophy
A study testing withdrawal of non-invasive ventilation in people with Myotonia, run by University Hospital, Grenoble at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myotonia
- What is being tested?
- withdrawal of non-invasive ventilation
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteFrance
- Study dates
- Jun 2008to Dec 2012
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%).
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
France.Functional Cardio-Respiratory Exploration Laboratory
Grenoble, Isere, 38000
Jean -Louis JL PEPIN, professor, 0033476765516, JPepin@chu-grenoble.fr
About this study
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.
Read more
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.
Read the detailed description
NIV is a technique of assisted ventilation that does not use the endotracheal route as the interface between the patient and the ventilator. NIV by positive pressure assistance involves ventilating the patient by means of a mask adjusted on the nose or covering the nose and mouth. This technique is now the recommended therapeutic strategy for the treatment of chronic alveolar hypoventilation. It improves survival and quality of life, and improves daytime blood gases in patients suffering form chronic restrictive respiratory failure.
For each check-up (3 visits), patients will have a polysomnography, a complete respiratory function measurement (Flows and lung volumes, CO2 sensitivity test, SNIF test, blood gazes analysis), a test of endothelial function (peripheral arterial tone), a test of arterial stiffness (pulse wave velocity), an assessment of systemic inflammation (ultra sensitive CRP, TNFa, IL6), assessment of diurnal vigilance tests ( OSLER test and sleepiness scale) and assessment of metabolic and endocrinal function (insulinemia, glucose blood level, Leptin, DHEA).
- Conditions
- Myotonia
- Being tested
- withdrawal of non-invasive ventilation
- Keywords
- endothelial function, peripheral arterial tone, systemic inflammation, oxidative stress, respiratory and peripheral muscular function
- Medical subject headings
- Myotonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
withdrawal of non-invasive ventilationOther
Four weeks withdrawal of non-invasive ventilation
| Study group | Role | What they receive |
|---|---|---|
| Myotonic Dystrophy 1 | Experimental | Not described Receives: Other: withdrawal of non-invasive ventilation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate endothelial dysfunction (as measured by Peripheral arterial tone (PAT)) and its evolution after four weeks withdrawal of non-invasive ventilation (NIV).
Measured: 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.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2008 (estimated)
- Study startJun 2008
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MyotoniaStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean Louis PEPIN, PROFESSOR, Principal investigator, University Hospital, Grenoble
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00745238
- Sponsor's protocol ID
- 0801
- Status last verified
- Sep 2008
- First submitted
- 1 Sep 2008
- Last updated
- 13 Aug 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Four Weeks Withdrawal of Non-invasive Ventilation (NIV) in Patients With Myotonic Dystrophy: Cardiovascular, Metabolic and Daytime Vigilance Induced Changes
- ClinicalTrials.gov ID
- NCT00745238
- Acronym / sponsor ID
- 0801
- Conditions
- Myotonia
- Keywords
- endothelial function, peripheral arterial tone, systemic inflammation, oxidative stress, respiratory and peripheral muscular function
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Study start
- Jun 2008
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 3 Sep 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
NIV is a technique of assisted ventilation that does not use the endotracheal route as the interface between the patient and the ventilator. NIV by positive pressure assistance involves ventilating the patient by means of a mask adjusted on the nose or covering the nose and mouth. This technique is now the recommended therapeutic strategy for the treatment of chronic alveolar hypoventilation. It improves survival and quality of life, and improves daytime blood gases in patients suffering form chronic restrictive respiratory failure.
For each check-up (3 visits), patients will have a polysomnography, a complete respiratory function measurement (Flows and lung volumes, CO2 sensitivity test, SNIF test, blood gazes analysis), a test of endothelial function (peripheral arterial tone), a test of arterial stiffness (pulse wave velocity), an assessment of systemic inflammation (ultra sensitive CRP, TNFa, IL6), assessment of diurnal vigilance tests ( OSLER test and sleepiness scale) and assessment of metabolic and endocrinal function (insulinemia, glucose blood level, Leptin, DHEA).
Study design
- Primary purpose
- Supportive care
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Myotonic Dystrophy 1 | Experimental | Other: withdrawal of non-invasive ventilation |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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%).
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| withdrawal of non-invasive ventilationFour weeks withdrawal of non-invasive ventilation | Other | Myotonic Dystrophy 1 |
Primary outcome
To evaluate endothelial dysfunction (as measured by Peripheral arterial tone (PAT)) and its evolution after four weeks withdrawal of non-invasive ventilation (NIV).
Time frame: 8 weeks
1 secondary outcome
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.
Time frame: 8 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2012.
- Background1-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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean Louis PEPIN, PROFESSOR principal investigator
University Hospital, Grenoble
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing withdrawal of non-invasive ventilation in people with Myotonia, run by University Hospital, Grenoble at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 13 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jean Louis PEPIN JP PEPIN, PROFESSOR (00330476765516, JPepin@chu-grenoble.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To evaluate endothelial dysfunction (as measured by Peripheral arterial tone (PAT)) and its evolution after four weeks withdrawal of non-invasive ventilation (NIV). (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00745238, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2012; AzTrials last refreshed its copy on 8 Nov 2026.