Abstract
Orthostatic hypotension (OH) and the co-existence with supine hypertension (SH) are debilitating consequences of autonomic failure in Parkinson’s disease (PD) and multiple system atrophy (MSA). Head-up tilt sleeping (HUTS) has the potential to treat both simultaneously. Within the Heads-Up trial, 20 persons with PD or MSA and both SH and OH were assigned randomly to two HUTS schemes with gradually increasing angles: 1° (placebo), 6° and 12°; or 6°, 12° and 18°. The effect of increasing the head of the bed (per cm) was analyzed with linear mixed models. HUTS did not reduce nocturnal SBP but improved other indicators of blood pressure control, including early morning supine SBP, nocturnal dipping profile, diurnal SBP and SBP fall upon standing, coinciding with improved orthostatic tolerance. Adherence was 100% at 6°, 80% at 12°, and 60% at 18°. Higher angles were more effective, but at the cost of lower tolerability. The trial is registered at ClinicalTrials.gov (NCT05551377, 19-09-2022).
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We would like to thank all patient researchers who were involved in developing the study and study materials, as well as all participants and their partners, for their efforts. We would also like to thank the late Prof. Dr. Gregor K. Wenning for being part of the Heads-Up consortium. This study was funded by the Michael J. Fox Foundation for Parkinson’s Research, grant number MJFF-020200. The funder played no role in study design, data collection, analysis and interpretation of data, or the writing of this manuscript. The study also received support from the Nico Job Beije Stichting for the development of study materials. The Radboudumc Centre of Expertise for Parkinson & Movement Disorders was supported by a center of excellence grant of the Parkinson’s Foundation.
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A.H.S., S.S., J.I., D.S., and Y.W. declare no competing interests. N.M.V. serves as associate editor of the Journal of Parkinson’s disease and receives funding from the Michael J. Fox Foundation for Parkinson’s Research, the Netherlands Organisation for Health Sciences and Development and from Verily Life Sciences. J.H.R. reports research grants from the Dutch Heart Foundation, EU Horizon-HLTH-2022. J.A.H.R.C. is editor for the Journal of Cerebral Blood Flow and Metabolism, has received funding by EFRO (European Fund for Regional Development), Alzheimer Nederland, the Netherlands Organisation for Health Research and Development, Health Holland, Gieskes-Strijbis Fund, has received speaker and consultancy fees from Eli Lilly and BMS, and is P.I. in the Dutch ABOARD consortium (Project ONBOARD | Alzheimer Nederland) in which several commercial parties participate. STB receives funding from the European Huntington’s Disease Network (EHDN) and Cure HD Initiative (CHDI), is involved in the EU Horizon 2020 project: Innovative Medicines Initiative (IMI) 2 (IDEA_FAST; grant agreement No 853981) and NWO NWA-ORC grant for the CureQ project (NWA.1389.20.244), and takes part in clinical trials sponsored by PRILENIA, PTC Therapeutics, WAVE, and VICO Therapeutics. LUMC has received consultancy fees from PTC Therapeutics, as Susanne T. de Bot is a member of the HD Expert Advisory Panel for the PTC518 phase 3 program (PTC Therapeutics). None of these sponsors was involved in the design, execution, interpretation, or writing of this study. A.F. reports royalties from Springer Verlag, speaker fees and honoraria from Antag Therapeutics, American Academy of Neurology, Austrian Neurology Society, Austrian Autonomic Society, Bial, Broadview Ventures, CNSystem, Desitin, Donau Krems University, Elsevier, GE Healthcare, Healthware International, International Parkinson Disease and Movement Disorders Society, KABEG, Medizin Forum, Medtronic, Prime Global, Sanofi, Theravance Biopharma, and research grants from the Austrian Science Fund, Medical University of Innsbruck, Mission MSA, Dr Johannes and Hertha Tuba Foundation and Austrian Exchange Program, outside of the present work. B.R.B. serves as the co-Editor in Chief for the Journal of Parkinson’s disease, serves on the editorial board of Practical Neurology and Digital Biomarkers, has received fees from serving on the scientific advisory board for the Critical Path Institute, Gyenno Science, MedRhythms, UCB, Kyowa Kirin and Zambon (paid to the Institute), has received fees for speaking at conferences from AbbVie, Bial, Biogen, GE Healthcare, Oruen, Roche, UCB and Zambon (paid to the Institute), and has received research support from Biogen, Cure Parkinson’s, Davis Phinney Foundation, Edmond J. Safra Foundation, Fred Foundation, Gatsby Foundation, Hersenstichting Nederland, Horizon 2020, IRLAB Therapeutics, Maag Lever Darm Stichting, Michael J Fox Foundation, Ministry of Agriculture, Ministry of Economic Affairs & Climate Policy, Ministry of Health, Welfare and Sport, Netherlands Organization for Scientific Research (ZonMw), Not Impossible, Parkinson Vereniging, Parkinson’s Foundation, Parkinson’s UK, Stichting Alkemade-Keuls, Stichting Parkinson NL, Stichting Woelse Waard, Health Holland/Topsector Life Sciences and Health, UCB, Verily Life Sciences, Roche and Zambon. B.R.B. does not hold any stocks or stock options with any companies that are connected to Parkinson’s disease or to any of his clinical or research activities. R.D.T. reports consultancy and speakers’ fees from Union Chimique Belge, Angellini, GlaxoSmithKline, Theravance Biopharma, LivAssured, Novartis, and Zogenix; and grants from the Dutch National Epilepsy Fund (EpilepsieNL), the Michael J Fox Foundation for Parkinson’s Research (MJFF-020200), Anna Teding van Berkhout Stichting, Medtronic, New Life Wearables, Vriendenloterij and the Netherlands Organisation for Health Research and Development (114025101).
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van der Stam, A.H., de Vries, N.M., Shmuely, S. et al. Tolerability and efficacy of full-body head-up tilt sleeping in Parkinson’s disease and multiple system atrophy. npj Parkinsons Dis. (2026). https://doi.org/10.1038/s41531-026-01359-y
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DOI: https://doi.org/10.1038/s41531-026-01359-y
