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A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening.
Sci Rep. 2021 10 05; 11(1):19734.SR

Abstract

Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation's ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360.

Authors+Show Affiliations

Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. Sleep and Health Zurich, University Center of Competence, University of Zurich, Zurich, Switzerland. Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.Department of Pharmaceutical Technology, Lokman Hekim University, Ankara, Turkey. Elixir Pharmaceutical Research and Development Corporation, Ankara, Turkey.Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.Elixir Pharmaceutical Research and Development Corporation, Ankara, Turkey. Department of Pharmaceutical Technology, Hacettepe University, Ankara, Turkey.Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.Institute of Forensic Medicine, University of Zurich, Zurich, Switzerland.Institute of Pharmacology and Toxicology, University of Zürich, Winterthurerstrasse 190, 8057, Zurich, Switzerland. landolt@pharma.uzh.ch. Sleep and Health Zurich, University Center of Competence, University of Zurich, Zurich, Switzerland. landolt@pharma.uzh.ch.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

34611208

Citation

Dornbierer, Dario A., et al. "A Novel Bedtime Pulsatile-release Caffeine Formula Ameliorates Sleep Inertia Symptoms Immediately Upon Awakening." Scientific Reports, vol. 11, no. 1, 2021, p. 19734.
Dornbierer DA, Yerlikaya F, Wespi R, et al. A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening. Sci Rep. 2021;11(1):19734.
Dornbierer, D. A., Yerlikaya, F., Wespi, R., Boxler, M. I., Voegel, C. D., Schnider, L., Arslan, A., Baur, D. M., Baumgartner, M. R., Binz, T. M., Kraemer, T., & Landolt, H. P. (2021). A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening. Scientific Reports, 11(1), 19734. https://doi.org/10.1038/s41598-021-98376-z
Dornbierer DA, et al. A Novel Bedtime Pulsatile-release Caffeine Formula Ameliorates Sleep Inertia Symptoms Immediately Upon Awakening. Sci Rep. 2021 10 5;11(1):19734. PubMed PMID: 34611208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A novel bedtime pulsatile-release caffeine formula ameliorates sleep inertia symptoms immediately upon awakening. AU - Dornbierer,Dario A, AU - Yerlikaya,Firat, AU - Wespi,Rafael, AU - Boxler,Martina I, AU - Voegel,Clarissa D, AU - Schnider,Laura, AU - Arslan,Aslihan, AU - Baur,Diego M, AU - Baumgartner,Markus R, AU - Binz,Tina Maria, AU - Kraemer,Thomas, AU - Landolt,Hans-Peter, Y1 - 2021/10/05/ PY - 2021/04/15/received PY - 2021/08/30/accepted PY - 2021/10/6/entrez PY - 2021/10/7/pubmed PY - 2021/12/31/medline SP - 19734 EP - 19734 JF - Scientific reports JO - Sci Rep VL - 11 IS - 1 N2 - Sleep inertia is a disabling state of grogginess and impaired vigilance immediately upon awakening. The adenosine receptor antagonist, caffeine, is widely used to reduce sleep inertia symptoms, yet the initial, most severe impairments are hardly alleviated by post-awakening caffeine intake. To ameliorate this disabling state more potently, we developed an innovative, delayed, pulsatile-release caffeine formulation targeting an efficacious dose briefly before planned awakening. We comprehensively tested this formulation in two separate studies. First, we established the in vivo caffeine release profile in 10 young men. Subsequently, we investigated in placebo-controlled, double-blind, cross-over fashion the formulation's ability to improve sleep inertia in 22 sleep-restricted volunteers. Following oral administration of 160 mg caffeine at 22:30, we kept volunteers awake until 03:00, to increase sleep inertia symptoms upon scheduled awakening at 07:00. Immediately upon awakening, we quantified subjective state, psychomotor vigilance, cognitive performance, and followed the evolution of the cortisol awakening response. We also recorded standard polysomnography during nocturnal sleep and a 1-h nap opportunity at 08:00. Compared to placebo, the engineered caffeine formula accelerated the reaction time on the psychomotor vigilance task, increased positive and reduced negative affect scores, improved sleep inertia ratings, prolonged the cortisol awakening response, and delayed nap sleep latency one hour after scheduled awakening. Based on these findings, we conclude that this novel, pulsatile-release caffeine formulation facilitates the sleep-to-wake transition in sleep-restricted healthy adults. We propose that individuals suffering from disabling sleep inertia may benefit from this innovative approach.Trials registration: NCT04975360. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/34611208/A_novel_bedtime_pulsatile_release_caffeine_formula_ameliorates_sleep_inertia_symptoms_immediately_upon_awakening_ L2 - https://doi.org/10.1038/s41598-021-98376-z DB - PRIME DP - Unbound Medicine ER -