Role of Sleep Apnea and Sympathetic Activity in Resistant Hypertensive Patients.

NCT01875341 | Completed Phase 3

• 1 other identifier: 2005972-01H
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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. 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. B. 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

Conditions

Type 2 Diabetes; Diabetic Nephropathy; Hypertension; Sleep Apnea

Keywords

type 2 diabetes; diabetic nephropathy; hypertension; sleep apnea; sympathetic hyperactivity

Outcome Measures

Primary Outcomes (1)

• 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

  baseline and 6 weeks post intervention

Secondary Outcomes (3)

• changes in daytime and night-time mean diastolic blood pressure

  baseline and post 6 weeks of therapy

• muscle sympathetic nerve activity -microneurography

  Baseline and 6 weeks post intervention

• plasma renin and aldosterone

  baseline to after 6 weeks

Study Arms (2)

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.

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.

Device: NCPAP; Nasal continuous positive airway pressure.; Device: NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group

Interventions

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.

Active treatment with NCPAP; Sub- active treatment with NCPAP

NCPAP Nasal Continuous Positive Airway Pressure-sub-therapeutic treatment group DEVICE

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.

Active treatment with NCPAP; Sub- active treatment with NCPAP

Eligibility Criteria

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

You may qualify if:

• 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)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead

Study Sites (1)

The Ottawa Hospital

Ottawa, Ontario, K1H 7W9, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetic Nephropathies; Hypertension; Sleep Apnea Syndromes

Interventions

Continuous Positive Airway Pressure

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Vascular Diseases; Cardiovascular Diseases; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Positive-Pressure Respiration; Respiration, Artificial; Airway Management; Therapeutics; Respiratory Therapy

Study Officials

• Marcel Ruzicka, Dr.

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Marcel Ruzicka

Study Record Dates

• First Submitted: June 4, 2013
• First Posted: June 11, 2013
• Study Start: December 1, 2004
• Primary Completion: February 1, 2015
• Study Completion: February 1, 2015
• Last Updated: February 10, 2015

Record last verified: 2015-02

Locations

CA (1)