Head-up Tilt Sleeping to Alleviate Orthostatic Hypotension, Supine Hypertension and Nocturia in Parkinson's Disease

Study Overview
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Brief Summary
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Autonomic dysfunction is common and often underrecognized in Parkinson's disease (PD). Orthostatic hypotension (OH) affects up to a third of PD patients and often coincides with supine hypertension. This co-occurrence complicates pharmacological treatment as treatment of one can negatively affect the other. Head-up tilt sleeping (HUTS) could improve both. This phase II randomized controlled trial (RCT) aims to investigate the efficacy and tolerability of this understudied intervention, leading to optimal implementation strategies.

Detailed Description
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Autonomic dysfunction is common and often underrecognized in Parkinson's disease (PD). Orthostatic hypotension (OH) affects up to a third of PD patients and about half of them also exhibit supine hypertension. In current clinical practice both are undertreated. The common co-occurrence of OH and supine hypertension complicates pharmacological treatment as improvement of one can be accomplished only at the expense of the other. Head-up tilt sleeping (HUTS) is the only intervention known that could improve both. The concept of HUTS is based on several small-scale observational studies and expert opinion. Although HUTS has been proposed as an effective and even first choice non-pharmacological treatment for OH for over three decades, it is often not advised to patients because of lack of evidence on its effectiveness and on how to implement it. The Heads-Up trial is a multicenter home-based double-blind phase II RCT. The study aims to investigate the efficacy and tolerability of HUTS, leading to optimal implementation strategies of HUTS to treat orthostatic hypotension and supine hypertension.

Official Title
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The Heads-Up Trial: Sleeping in a Head-Up Tilt Position to Alleviate Orthostatic Hypotension, Supine Hypertension and Nocturia in Parkinson's Disease

Conditions
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Parkinson Disease, Parkinsonism

Intervention / Treatment
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* Other: Head-up tilt sleeping


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Orthostatic hypotension defined as a systolic BP decrease of ≥20 mmHg, or a diastolic decrease of ≥10 mmHg, within 3 min after changing from a supine to standing position OR mean standing BP of ≤75 mmHg (marker for symptomatic orthostatic hypotension). In patients with supine hypertension, a decrease in systolic BP of ≥ 30 mmHg is required; Orthostatic intolerance: direct complaints (dizziness, blurry vision, etc.) and/or indirect signs (falls or freezing episodes that relate to postural challenge); Supine hypertension defined as a systolic BP of ≥140 mmHg, and/or diastolic of ≥90 mmHg, after 5 min of supine rest; Idiopathic PD or parkinsonism (multiple system atrophy, progressive supranuclear palsy, corticobasal degeneration, vascular parkinsonism and Lewy body dementia); Ability to walk (with or without a walking aid), as subjectively determined by the researcher; Stable medication regimens for orthostatic hypotension and supine hypertension during the trial; Exclusion Criteria: Inability to follow instructions and complete questionnaires, as assessed by the researcher;

Ages Eligible for Study
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Minimum Age: 18 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: Parallel Assignment
Interventional Model Description: Participants are divided into two groups, the intervention and control (delayed intervention) group.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br>At T0, in-clinic inclusion, we will record basic characteristics and several questionnaires, we will also perform a short tilt-table-test and standing blood pressure (BP) test. Intake is followed by one week of horizontal sleeping for baseline home-based BP measurements. Participants in the intervention group will then sleep in a head-up tilt position for two weeks each in angles 6°, 12° and 18°. At the second and final in-clinic meeting, at T1, measurements done at T0 will be repeated, complemented with an assessment of barriers and facilitators of HUTS. During HUTS daily BP measurements will be done, and data will be collected on orthostatic tolerance, nighttime urine production, subjective comfort of HUTS, falls. | Other: Head-up tilt sleeping<br>* Whole-body head-up tilt sleeping (HUTS) will be carried out in three different angles, each for the duration of two weeks. Prior to the first angle the participant will sleep in a horizontal position for 1 week. The different angles will be installed using a wedge between the mattress and bed frame.<br>|
| Other: Delayed intervention group<br>Follows the same structure as the intervention group, but starts with a HUTS placebo angle of 1° for two weeks, followed by two intervention angles of 6° and 12° for two weeks each. The 1°-angle serves as the control intervention. | Other: Head-up tilt sleeping<br>* Whole-body head-up tilt sleeping (HUTS) will be carried out in three different angles, each for the duration of two weeks. Prior to the first angle the participant will sleep in a horizontal position for 1 week. The different angles will be installed using a wedge between the mattress and bed frame.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average overnight supine blood pressure | Average overnight supine blood pressure (mmHg) from the 24h ambulatory blood pressure measurement (ABPM) | Measured four times: in week 1, 3, 5 and 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Daily supine blood pressure | Supine blood pressure (mmHg) measured every morning directly after awakening before getting out of bed | Daily in week 1 up to and including week 7 | 
| Orthostatic blood pressure | Standing orthostatic blood pressure test (mmHg). Measured in clinic and home-based guided by a researcher via video call. | Measured six times: in-clinic (T0; pre-intervention), in week 1, 3, 5 and 7, and in-clinic on the day after week 7 ends (T1; post-intervention) | 
| 24h ABPM parameters | 24h ABPM parameters blood pressure variability (mmHg), nocturnal blood pressure dipping (mmHg) and average daytime blood pressure (mmHg). Each of these measures will be derived from the 24 hour blood pressure measurements, and reported separately. | In week 1, 3, 5 and 7 | 
| Orthostatic tolerance | Self-reported burden of symptoms of orthostatic hypotension (Orthostatic hypotension questionnaire (OHQ)). The score ranges from 0 to 100, with a higher number meaning worse symptoms of orthostatic hypotension. | Week 1, 3, 5 and 7 | 
| Nocturia | Self-reported frequency of daytime and night time urination and impact on quality of life (International Consultation on Incontinence Questionnaire Nocturia Module (ICIQ-N)) | Week 1, 3, 5 and 7 | 
| Subjective comfort of HUTS (head up tilted sleeping) | Self-reported tolerability of the head up tilted sleeping at different angles including questions about sleep duration, sleep quality and comfort, and feeling rested in the morning. | Week 1, 3, 5 and 7 | 
| Falls | Self-reported falls and in case of a fall additional questions about the time and circumstances | Week 1, 3, 5 and 7 | 
| Overnight change in body weight | Weight (kg) difference between the evening and the morning, both measured after micturition | Daily in week 1 up to and including week 7 | 
| Nighttime urine production | Urine volume measured in a urinal (ml) | Week 1, 3, 5 and 7 | 
| Barriers and facilitators of the intervention | Structured interview | Immediately post-intervention (day after week 7, T1) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson's disease, Orthostatic hypotension, Supine hypertension, Autonomic dysfunction