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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson Disease; Parkinsonism
• Intervention / Treatment: Other: Head-up tilt sleeping

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Radboudumc
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands, 2333 ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group; 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; 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.
Other: Delayed intervention group; 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; 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.

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Timed up and go test (TUG)	Measurement of the time that the participant takes to rise from a chair, walk three meters, turn around 180 degrees, walk back to the chair, and sit down while turning 180 degrees	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Symptoms of Parkinson's disease	Movement disorders society unified disease rating scale (MDS-UPDRS). Scores range from 0 to 199, with a higher score indicating a more severe impairment related to Parkinson's disease.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Quality of sleep	Pittsburgh Sleep Quality Index (PSQI). Score ranges from 0 to 21, with 21 indicating a worse sleep quality.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Fear of falling	Falls Efficacy Scale (FES). Scores ranges from 16 to 67, with a higher score meaning a worse fear of falling.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Subjective level of physical activity	Longitudinal Aging Study Amsterdam (LASA) Physical Activity Questionnaire (LAPAQ). Score corresponds to time spend doing physical activities. A higher score indicates a more active last two weeks.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Cardiovascular autonomic symptoms	Selected cardiovascular questions from the Scales for Outcomes in Parkinson's Disease - Autonomic Dysfunction (SCOPA-AUT). Scored 0 to 9, a worse score means more symptoms of orthostatic hypotension.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Experienced quality of life	Quality of life questionnaire: the Parkinson's disease questionnaire (PDQ-39). Scores range from 0 to 100, with a higher score indicating a worse quality of life.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Experienced anxiety and depression	Quality of life questionnaire: the hospital anxiety and depression scale (HADS). Scores range from 0 to 21 for depression and anxiety, a score between 0-7 means no anxiety or depression, 8-14 possibility of an anxiety or depressive disorder and 15-21 likely a depressive or anxiety disorder.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)
Mental health	Quality of life questionnaire: the Mental Health Continuum-Short Form (MHC-SF). Scores range from 0 to 70, with a higher score meaning a better emotional wellbeing.	Pre-intervention (day before week 1, T0) and post-intervention (day after week 7,T1)

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Collaborators: Leiden University Medical Center; Michael J. Fox Foundation for Parkinson's Research
• Investigators: Principal Investigator: Roland D Thijs, MD, PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2023
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: September 7, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Actual): May 9, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Parkinson's disease; Orthostatic hypotension; Autonomic dysfunction; Supine hypertension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Lower Urinary Tract Symptoms; Urological Manifestations; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Hypertension; Parkinson Disease; Hypotension; Parkinsonian Disorders; Hypotension, Orthostatic; Nocturia
• Other Study ID Numbers: NL.80610.091.22; MJFF-020200 (Other Grant/Funding Number: Michael J Fox Foundation for Parkinson's Research)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Relevant and anonymized research data will be shared in the validated research database DANS Easy (Data Archiving and Networked Services). It will also be shared with the funding foundation (MJFF).
• IPD Sharing Time Frame: Study protocol and statistical analysis plan are shared with the funding foundation prior to the onset of the study. After completion of the measurements and analysis we will share the clinical study report with the funding foundation and place relevant and anonymized data on the DANS Easy database.
• IPD Sharing Access Criteria: Access to the data is restricted, meaning that researchers who are interested in re-use of the data are asked to contact the central contact person for permission. Approval is given after a signed agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No