Insomnia Prevalence and Treatment Impact on Systemic Hypertension

Study Overview
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Brief Summary
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Insomnia is defined as some difficulty in sleep onset, consolidation, duration, or quality, despite appropriate opportunities for getting sleep. In the last decade, there is growing evidence associating insomnia and high blood pressure, (HBP), coronary disease, heart failure, atrial fibrillation, as well as with an increased mortality rate. Despite the previously mentioned advances, the real impact of insomnia on HBP is unknown. It is unclear whether the diagnosis and pharmacologic treatment of insomnia will have an impact on 24-h BP. The aim of this study is to outline the prevalence of insomnia in patients with HBP followed in the ambulatories from the Hypertension Units at InCor and Hospital das Clínicas. The main hypothesis is that the prevalence of insomnia is high and most patients remain undiagnosed and consequently untreated. For this phase, up to 1,500 patients with HBP will be selected. Besides the medical records with demographic and anthropometric data, personal and familiar background, as well as regular medication, all patients will perform three systematic and standardized blood pressure checks on electric monitors.

Detailed Description
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Prevalence of insomnia in patients with HBP The aim of this study is to outline the prevalence of insomnia in patients with HBP followed by the outpatients' clinics at the InCor and Hospital das Clínicas. The main hypothesis is that the prevalence of insomnia is high and most patients remain undiagnosed and consequently untreated. For this phase, up to 1,500 patients with HBP will be recruited. Besides the medical records with demographic and anthropometric data, personal and familiar background, as well as regular medication, all patients will perform three systematic and standardized blood pressure checks on electric monitors. The average of the second and third checks will be the final result. Furthermore, the following exams will be made: Definition of the presence of insomnia following the criteria from DSM V and filling up the insomnia severity index. Evaluation of the Pittsburgh Sleep Quality Index. Evaluation of obstructive sleep apnea by NoSAS score. Evaluation of daytime sleepiness by the Epworth Sleepiness Scale. Filling the DDAS form for evaluation of perception and impact of insomnia on the life of HBP patients. Filling the Beck form for depression evaluation. The clinical characteristics of HBP patients with and without insomnia will be compared testing the hypothesis that patients with insomnia will be under more blood pressure medications and/or uncontrolled bllod pressure than patients without insomnia. If positive, a multivariate analysis will be performed for adjusting for counfonding factors.

Official Title
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Insomnia Prevalence and Treatment Impact on Systemic Hypertension

Conditions
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Insomnia, Hypertension

Intervention / Treatment
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* Drug: Ramelteon (RozeremR)
* Behavioral: sleep hygiene


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: BMI <40Kg/m2; Availability to participate History of HBP under regular treatment (systolic pressure between 130-160 and diastolic pressure between 80-100 mmHg). Exclusion criteria: Use of benzodiazepines or Z drugs; Night workers; History of severe chronic obstructive pulmonary disease (COPD); Heart failure (ejection fraction <40% on echocardiogram); Prior stroke; Generalized anxiety disorder (GAD-7 >14 points) and severe depression (Beck); Severe liver disease; Alcohol abuse; Advanced chronic kidney disease 4 or 5 (glomerular filtration rate <30ml/min/1.73m2); Patient who is on loop diuretics; Patient with type 1 diabetes; Patient with decompensated type 2 diabetes (Glycated hemoglobin >8%); Urinuria Incontinence; Prostatism; History of active cancer; Pregnancy; Complex sleep behaviors, suicidal behavior; Other formal labeled contraindications, including a history of angioedema with ramelteone and patients using fluvoxamine (a strong inhibitor of CYP1A2)

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Control Group<br>Sleep hygiene alone (control group) | Behavioral: sleep hygiene<br>* sleep behavioral guidelines<br>|
| Other: Intervention Group<br>Sleep Hygiene and Ramelteone (RozeremTM) 8 mg at night | Drug: Ramelteon (RozeremR)<br>* 8mg daily<br>Behavioral: sleep hygiene<br>* sleep behavioral guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of insomnia treatment on blood pressure (evaluated by Ambulatory blood pressure monitoring) | To assess the impact of treatment of early insomnia with ramelteon on daytime and nighttime blood presure (in mmHg) in hypertensive patients on 24-hour evaluation of ambulatory blood pressure monitoring. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of insomnia treatment on blood pressure (evaluated by office blood pressure) | To evaluate the impact of treating initial insomnia with ramelteone on office blood pressure in hypertensive patients on office blood pressure (in mmHg) | 3 months | 
| Efficacy of insomnia treatment on Sleep duration | To assess the impact of treating insomnia with ramelteon in hypertensive patients on sleep duration evaluated by actigraphy (and reported in minutes of sleep); | 3 months | 
| Efficacy of insomnia treatment on sleep quality | To evaluate the impact of treating insomnia with ramelteon in hypertensive patients on sleep quality; | 3 months | 
| Efficacy of insomnia treatment on subgroups of patients (intending to be a sub-study) | Assess whether the pressure response of insomnia treatment on the primary and secondary outcomes is mediated by the presence of obstructive sleep apnea. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insomnia, hypertension, Ramelteon, sleep hygiene