Type 2 DiabetesPhase 3SASNCT01875341
Role of Sleep Apnea and Sympathetic Activity in Resistant Hypertensive Patients.
A Phase 3 study testing NCPAP; Nasal continuous positive airway pressure. and NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group in people with Type 2 Diabetes and Diabetic Nephropathy, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
Hypertension is highly prevalent in type 2 diabetic patients (NIDDM) with nephropathy, and is the single most important determinant of the rate of renal function loss. In many of these patients, hypertension is resistant to therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes, Diabetic Nephropathy, Hypertension
- What is being tested?
- NCPAP; Nasal continuous positive airway pressure. and NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- Dec 2004to Feb 2015
- Phase
- Phase 3
- 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
- Males and females 18 years or older
- On 3 or more antihypertensive medications with resistant hypertension of >140/90 mmHg (resting) despite treatment
- Diagnosis of sleep apnea (15 apneic/hypopneic episodes per hour and a score of 10 on Epworth sleepiness scale).
- Creatinine clearance > 20 ml/min with microalbuminuria or proteinuria, (results within past 6 months)
Who cannot join
- Acute coronary syndrome within 6 months
- Patients with clinically documented congestive heart failure
- Patients with relevant cardiac arrhythmias (second and third-degree heart block or premature ventricular complexes in Lown classes IV or V)
- Pregnant or lactating women
- Patients with leg injury involving nerve damage
- Patients with symptomatic peripheral neuropathy
Show all 14Show fewer
- Patients with predominant central sleep apnea
- Patients mentally unable to give informed consent
- Professional drivers
- Patients with a resting blood pressure >180/110 mmHg
- Patients taking clonidine
- Patients with sleep apnea causing daily drowsiness
- Patients with severe hyperkalemia (>5.5 mmol/L) or hypokalemia (<3.3 mmol/L)
- Patients with a BMI of >35
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Resistant Hypertension in Patient With Diabetic Nephropathy: Role of Sleep Apnea and Associated Sympathetic Hyperactivity.
Hypertension is highly prevalent in type 2 diabetic patients (NIDDM) with nephropathy, and is the single most important determinant of the rate of renal function loss. In many of these patients, hypertension is resistant to therapy. Although increased sympathetic activity is also highly prevalent in NIDDM patients with nephropathy and chronic renal insufficiency, little attention has been paid to sleep apnea as the cause of both resistant hypertension and sympathetic hyperactivity in this population. Since the prevalence of sleep apnea is increased in patients with either NIDDM, or resistant hypertension, or chronic renal insufficiency, it is almost certain that sleep apnea has a high prevalence in patients in whom all three states co-exist, i.e. NIDDM patients with nephropathy and hypertension resistant to therapy. As a consequence of undetected and untreated sleep apnea, resistant hypertension, nocturnal hypertension, and sympathetic hyperactivity likely contribute to accelerated loss of renal function and increased cardiovascular morbidity and mortality in these patients.
Hypothesis: A. Sleep apnea is highly prevalent in type 2 diabetic patients with diabetic nephropathy and hypertension resistant to therapy. Treatment with nasal continuous positive airway pressure (NCPAP) will result in a decrease in blood pressure and restore normal diurnal blood pressure pattern.
Read more
- Sleep apnea-caused hypertension is mediated by sympathetic hyperactivity and increased activity of the renin-angiotensin-aldosterone system (RAAS) in type 2 diabetic patients with nephropathy. A decrease in sympathetic hyperactivity in response to NCPAP therapy will result in a decrease in plasma renin activity and plasma aldosterone concomitant with decreases in blood pressure.
Randomized, double blind, parallel comparative (two groups) one center trial.
Therapeutic treatment with nasal continuous positive airway pressure (NCPAP) Sub-therapeutic treatment with nasal continuous positive airway pressure
Read the detailed description
The study will be double blind and consist of two parallel groups. Patients with type 2 diabetes with a creatinine clearance above 20 ml/min and with microalbuminuria or proteinuria who have both resistant hypertension and sleep apnea will be studied. Creatinine clearance and proteinuria will be assessed from a 24 hour urine collection not older than 6 months. Microalbuminuria will be assessed from at least 2 out of 3 positive random urine samples with the last one not older than 6 months. Blood pressure will be considered as resistive to treatment if the patient is on 3 or more antihypertensive medications with blood pressure readings of greater than 140/90 mmHg on the last 2 out of 3 office visits. Sleep apnea syndrome will be defined by the presence of at least 5 apneic or hypopneic episodes per hour during an overnight sleep study.
Screening will be done in the following manner: Patients seen in the Hypertension Unit at the University of Ottawa Heart Institute, General Nephrology Clinic and Progressive Renal Insufficiency Clinic at the Ottawa Hospital, will be screened by the study coordinator. For the patients who meet the study criteria, the attending physician is asked for permission to contact each patient. If patients agree to participate, they will undergo a sleep study. Screening of patients and subsequent sleep studies will continue until 54 consecutive patients with moderate to severe sleep apnea (15 apneic or hypopneic episodes per hr) are found and enrolled into the study. The prevalence of sleep apnea in the specialty clinic population will be calculated as the number of patients with sleep apnea diagnosed based on a sleep study divided by the total number of clinic patients screened who underwent a sleep study.
After the baseline visit and completion of all preliminary procedures, specific studies for microneurography, plasma renin and aldosterone will be performed. Consequently, a 24 hour blood pressure monitor and a 24 hour urine collection for creatinine clearance, microalbuminuria and proteinuria will be done. Once all the testing has been completed, the patient will be randomized to therapeutic or sub-therapeutic treatment with nasal continuous positive airway pressure for 6 weeks. After 6 weeks of treatment the specific studies, 24 hour blood pressure monitoring and 24 hour urine collection will be repeated.
- Conditions
- Type 2 Diabetes, Diabetic Nephropathy, Hypertension, Sleep Apnea
- Being tested
- NCPAP; Nasal continuous positive airway pressure., NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group
- Keywords
- type 2 diabetes, diabetic nephropathy, hypertension, sleep apnea, sympathetic hyperactivity
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetic Nephropathies, Hypertension, Sleep Apnea Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NCPAP; Nasal continuous positive airway pressure.Device
Patients will be randomized to receive either therapeutic or sub-therapeutic NCPAP; Nasal continuous positive airway pressure treatment. In patients randomized to therapeutic NCPAP, treatment pressures will be increased until apneas and hypopneas are prevented during all sleep stages. In the sub-therapeutic treatment group, pressure will be left unchanged at the lowest possible value for the NCPAP device. Pressure settings for NCPAP therapy will be determined by Dr. J. Leech, collaborator and specialist in sleep disorders. Treatment will be continued for a total of 6 weeks.
NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment groupDevice
In the sub-therapeutic treatment group, pressure will be left unchanged at the lowest possible value for the NCPAP device. Pressure settings for NCPAP therapy will be determined by Dr. J. Leech, collaborator and specialist in sleep disorders. Treatment will be continued for a total of 6 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Active treatment with NCPAP | Active comparator | This group will receive treatment with NCPAP, Nasal Continuous Positive Airway Pressure for 6 weeks. Nasal Continuous Positive Airway Pressures will be increased until apneas \& hypopneas are prevented during all sleep stages. Receives: Device: NCPAP; Nasal continuous positive airway pressure.; Device: NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group |
| Sub- active treatment with NCPAP | Sham comparator | This group will receive treatment with Nasal Continuous Positive Airway Pressure at sub-therapeutic levels for 6 weeks. Patients will be taught how to use NCPAP in the sleep lab. Pressures will be left unchanged at the lowest possible value for the NCPAP device. After completion of treatment patients will be provided usual NCPAP therapy. Receives: Device: NCPAP; Nasal continuous positive airway pressure.; Device: NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary end-point: change in daytime and night-time mean systolic blood pressure
Blood pressures will be assessed by 24 hour ambulatory blood pressure monitoring (ABPM) from baseline to after 6 weeks of therapy in the two treatment groups
Measured: baseline and 6 weeks post intervention
Secondary outcomes (3)
changes in daytime and night-time mean diastolic blood pressure
Blood pressures will be assessed by 24 hour blood pressure monitoring
Measured: baseline and post 6 weeks of therapy
muscle sympathetic nerve activity -microneurography
microneurography,will assess sympathetic hyperactivity measuring Muscle sympathetic-nerve activity from the peroneal nerve. A tungsten micro electrode will be inserted into the peroneal nerve. A reference electrode will be placed subcutaneously 1 to 2 cm from the recording electrode. The sympathetic activity will be amplified, filtered, integrated and displayed on a computer monitor. In addition, the signal will be digitized and recorded on a computer with a sampling rate of 2,000 Hz. All recordings will be done in a similar manner after at least 20 minutes of rest and will be combined with continuous blood pressure and heart rate measurements.
Muscle sympathetic-nerve activity will be expressed as the number of bursts per minute and as the number of bursts per 100 heart beats, to correct for differences in heart rate.
Measured: Baseline and 6 weeks post intervention
plasma renin and aldosterone
serum renin and aldosterone levels will be drawn after 30 minutes of rest . All samples will be collected in the appropriate tubes, shielded from the light and immediately placed on ice. Samples will be processed and stored at -80°C for analysis at a later date.
Plasma renin activity will be assessed by radioimmunoassay (RIA). Plasma aldosterone will be assessed by RIA after separation by High-performance liquid chromatography (HPLC)
Measured: baseline to after 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2013 (estimated)
- Study startDec 2004
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Marcel Ruzicka, Ottawa Hospital Research Institute
- Investigators
- Marcel Ruzicka, Dr., Principal investigator, Ottawa Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01875341
- Sponsor's protocol ID
- 2005972-01H
- Acronym
- SAS
- Status last verified
- Feb 2015
- First submitted
- 4 Jun 2013
- Last updated
- 10 Feb 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Resistant Hypertension in Patient With Diabetic Nephropathy: Role of Sleep Apnea and Associated Sympathetic Hyperactivity.
- ClinicalTrials.gov ID
- NCT01875341
- Acronym / sponsor ID
- SAS / 2005972-01H
- Conditions
- Type 2 Diabetes, Diabetic Nephropathy, Hypertension, Sleep Apnea
- Keywords
- type 2 diabetes, diabetic nephropathy, hypertension, sleep apnea, sympathetic hyperactivity
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- Dec 2004
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (actual)
- First posted
- 11 Jun 2013 (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.
Hypertension is highly prevalent in type 2 diabetic patients (NIDDM) with nephropathy, and is the single most important determinant of the rate of renal function loss. In many of these patients, hypertension is resistant to therapy. Although increased sympathetic activity is also highly prevalent in NIDDM patients with nephropathy and chronic renal insufficiency, little attention has been paid to sleep apnea as the cause of both resistant hypertension and sympathetic hyperactivity in this population. Since the prevalence of sleep apnea is increased in patients with either NIDDM, or resistant hypertension, or chronic renal insufficiency, it is almost certain that sleep apnea has a high prevalence in patients in whom all three states co-exist, i.e. NIDDM patients with nephropathy and hypertension resistant to therapy. As a consequence of undetected and untreated sleep apnea, resistant hypertension, nocturnal hypertension, and sympathetic hyperactivity likely contribute to accelerated loss of renal function and increased cardiovascular morbidity and mortality in these patients.
Hypothesis: A. Sleep apnea is highly prevalent in type 2 diabetic patients with diabetic nephropathy and hypertension resistant to therapy. Treatment with nasal continuous positive airway pressure (NCPAP) will result in a decrease in blood pressure and restore normal diurnal blood pressure pattern.
- Sleep apnea-caused hypertension is mediated by sympathetic hyperactivity and increased activity of the renin-angiotensin-aldosterone system (RAAS) in type 2 diabetic patients with nephropathy. A decrease in sympathetic hyperactivity in response to NCPAP therapy will result in a decrease in plasma renin activity and plasma aldosterone concomitant with decreases in blood pressure.
Randomized, double blind, parallel comparative (two groups) one center trial.
Therapeutic treatment with nasal continuous positive airway pressure (NCPAP) Sub-therapeutic treatment with nasal continuous positive airway pressure
Detailed description
The study will be double blind and consist of two parallel groups. Patients with type 2 diabetes with a creatinine clearance above 20 ml/min and with microalbuminuria or proteinuria who have both resistant hypertension and sleep apnea will be studied. Creatinine clearance and proteinuria will be assessed from a 24 hour urine collection not older than 6 months. Microalbuminuria will be assessed from at least 2 out of 3 positive random urine samples with the last one not older than 6 months. Blood pressure will be considered as resistive to treatment if the patient is on 3 or more antihypertensive medications with blood pressure readings of greater than 140/90 mmHg on the last 2 out of 3 office visits. Sleep apnea syndrome will be defined by the presence of at least 5 apneic or hypopneic episodes per hour during an overnight sleep study.
Screening will be done in the following manner: Patients seen in the Hypertension Unit at the University of Ottawa Heart Institute, General Nephrology Clinic and Progressive Renal Insufficiency Clinic at the Ottawa Hospital, will be screened by the study coordinator. For the patients who meet the study criteria, the attending physician is asked for permission to contact each patient. If patients agree to participate, they will undergo a sleep study. Screening of patients and subsequent sleep studies will continue until 54 consecutive patients with moderate to severe sleep apnea (15 apneic or hypopneic episodes per hr) are found and enrolled into the study. The prevalence of sleep apnea in the specialty clinic population will be calculated as the number of patients with sleep apnea diagnosed based on a sleep study divided by the total number of clinic patients screened who underwent a sleep study.
After the baseline visit and completion of all preliminary procedures, specific studies for microneurography, plasma renin and aldosterone will be performed. Consequently, a 24 hour blood pressure monitor and a 24 hour urine collection for creatinine clearance, microalbuminuria and proteinuria will be done. Once all the testing has been completed, the patient will be randomized to therapeutic or sub-therapeutic treatment with nasal continuous positive airway pressure for 6 weeks. After 6 weeks of treatment the specific studies, 24 hour blood pressure monitoring and 24 hour urine collection will be repeated.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active treatment with NCPAP | Active comparator | Device: NCPAP; Nasal continuous positive airway pressure., Device: NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment groupThis group will receive treatment with NCPAP, Nasal Continuous Positive Airway Pressure for 6 weeks. Nasal Continuous Positive Airway Pressures will be increased until apneas \& hypopneas are prevented during all sleep stages. |
| Sub- active treatment with NCPAP | Sham comparator | Device: NCPAP; Nasal continuous positive airway pressure., Device: NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment groupThis group will receive treatment with Nasal Continuous Positive Airway Pressure at sub-therapeutic levels for 6 weeks. Patients will be taught how to use NCPAP in the sleep lab. Pressures will be left unchanged at the lowest possible value for the NCPAP device. After completion of treatment patients will be provided usual NCPAP therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males and females 18 years or older
- On 3 or more antihypertensive medications with resistant hypertension of >140/90 mmHg (resting) despite treatment
- Diagnosis of sleep apnea (15 apneic/hypopneic episodes per hour and a score of 10 on Epworth sleepiness scale).
- Creatinine clearance > 20 ml/min with microalbuminuria or proteinuria, (results within past 6 months)
Key exclusion criteria (14 listed)
- Acute coronary syndrome within 6 months
- Patients with clinically documented congestive heart failure
- Patients with relevant cardiac arrhythmias (second and third-degree heart block or premature ventricular complexes in Lown classes IV or V)
- Pregnant or lactating women
- Patients with leg injury involving nerve damage
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 |
|---|---|---|
| NCPAP; Nasal continuous positive airway pressure.Patients will be randomized to receive either therapeutic or sub-therapeutic NCPAP; Nasal continuous positive airway pressure treatment. In patients randomized to therapeutic NCPAP, treatment pressures will be increased until apneas and hypopneas are prevented during all sleep stages. In the sub-therapeutic treatment group, pressure will be left unchanged at the lowest possible value for the NCPAP device. Pressure settings for NCPAP therapy will be determined by Dr. J. Leech, collaborator and specialist in sleep disorders. Treatment will be continued for a total of 6 weeks. | Device | Active treatment with NCPAP, Sub- active treatment with NCPAP |
| NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment groupIn the sub-therapeutic treatment group, pressure will be left unchanged at the lowest possible value for the NCPAP device. Pressure settings for NCPAP therapy will be determined by Dr. J. Leech, collaborator and specialist in sleep disorders. Treatment will be continued for a total of 6 weeks. | Device | Active treatment with NCPAP, Sub- active treatment with NCPAP |
Primary outcome
Primary end-point: change in daytime and night-time mean systolic blood pressure
Time frame: baseline and 6 weeks post intervention
Blood pressures will be assessed by 24 hour ambulatory blood pressure monitoring (ABPM) from baseline to after 6 weeks of therapy in the two treatment groups
3 secondary outcomes
changes in daytime and night-time mean diastolic blood pressure
Time frame: baseline and post 6 weeks of therapy
muscle sympathetic nerve activity -microneurography
Time frame: Baseline and 6 weeks post intervention
plasma renin and aldosterone
Time frame: baseline to after 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2015.
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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.
Marcel Ruzicka, Dr. principal investigator
Ottawa Hospital Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NCPAP; Nasal continuous positive airway pressure. and NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group in people with Type 2 Diabetes and Diabetic Nephropathy, run by Ottawa Hospital Research Institute at 1 site in Canada.
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 14 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: finished, as of the sponsor's last update on 10 Feb 2015. 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 Canada. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary end-point: change in daytime and night-time mean systolic blood pressure (time frame: baseline and 6 weeks post intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Feb 2015.