Study protocol for the Heads-Up trial: a phase II randomized controlled trial investigating head-up tilt sleeping to alleviate orthostatic intolerance in Parkinson’s Disease and parkinsonism

BMC Neurology, vol. 24, pp. 4

Abstract

BACKGROUND: In persons with Parkinson's Disease (PD) or certain forms of atypical parkinsonism, orthostatic hypotension is common and disabling, yet often underrecognized and undertreated. About half of affected individuals also exhibit supine hypertension. This common co-occurrence of both orthostatic hypotension and supine hypertension complicates pharmacological treatments as the treatment of the one can aggravate the other. Whole-body head-up tilt sleeping (HUTS) is the only known intervention that may improve both. Evidence on its effectiveness and tolerability is, however, lacking, and little is known about the implementability. METHODS: In this double-blind multicenter randomized controlled trial (phase II) we will test the efficacy and tolerability of HUTS at different angles in 50 people with PD or parkinsonism who have both symptomatic orthostatic hypotension and supine hypertension. All participants start with one week of horizontal sleeping and subsequently sleep at three different angles, each maintained for two weeks. The exact intervention will vary between the randomly allocated groups. Specifically, the intervention group will consecutively sleep at 6°, 12° and 18°, while the delayed treatment group starts with a placebo angle (1°), followed by 6° and 12°. We will evaluate tolerability using questionnaires and compliance to the study protocol. The primary endpoint is the change in average overnight blood pressure measured by a 24-hour ambulatory blood pressure recording. Secondary outcomes include orthostatic blood pressure, orthostatic tolerance, supine blood pressure, nocturia and various other motor and non-motor tests and questionnaires. DISCUSSION: We hypothesize that HUTS can simultaneously alleviate orthostatic hypotension and supine hypertension, and that higher angles of HUTS are more effective but less tolerable. The Heads-Up trial will help to clarify the effectiveness, tolerability, and feasibility of this intervention at home and can guide at-home implementation. TRIAL REGISTRATION: ClinicalTrials.gov NCT05551377; Date of registration: September 22, 2022.

Authors 10

1. Amber H. van der Stam corresponding Aachen Department of Neurology, Leiden University Medical Centre

   Leiden University · Radboud University Nijmegen · Leiden University Medical Center · Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands. Amber.vanderStam@radboudumc.nl

   Donders Institute for Brain Cognition and Behavior, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands. Amber.vanderStam@radboudumc.nl

   Donders Institute for Brain Cognition and Behavior, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands

2. Nienke M. de Vries

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain Cognition and Behavior, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands

3. Sharon Shmuely

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain Cognition and Behavior, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands

4. Daan Smeenk

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain Cognition and Behavior, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands

5. Joost H.W. Rutten

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Internal medicine, Division of Vascular medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

6. Ineke A. van Rossum Aachen Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

7. Susanne Tamara de Bot Aachen Department of Neurology, Leiden University Medical Centre

   Leiden University · Leiden University Medical Center

   Affiliation as printed

   Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

8. Jurgen A.H.R. Claassen

   Radboud University Nijmegen · Radboud University Medical Center

   Affiliation as printed

   Department of Geriatric medicine, Radboud University Medical Centre, Nijmegen, The Netherlands

9. Bastiaan R. Bloem

   Radboud University Medical Center · Donders Institute for Brain, Cognition and Behaviour

   Affiliation as printed

   Donders Institute for Brain Cognition and Behavior, Department of Neurology, Center of Expertise for Parkinson & Movement Disorders, Radboud University Medical Centre, Nijmegen, The Netherlands

10. Roland D. Thijs Aachen Department of Neurology, Leiden University Medical Centre

    Leiden University · Leiden University Medical Center · Stichting Epilepsie Instellingen Nederland · UCL Queen Square Institute of Neurology · University College London

    Affiliation as printed

    Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands

    Stichting Epilepsie Instellingen Nederland (SEIN), Hoofddorp, The Netherlands

    UCL Queen Square Institute of Neurology, University College London, London, UK