DoCTR News Research

SWIPED trial will leverage propofol to probe relationships of slow-wave sleep, depression, and cognitive dysfunction

Ben Palanca, MD, PhD, MSc, Associate Professor of Anesthesiology and Psychiatry and Eric J. Lenze, MD, Wallace and Lucille K. Renard Professor and head of the Department of Psychiatry at Washington University School of Medicine in St. Louis, have received a $703,237 grant from the National Institute of Mental Health (NIMH) to begin the Slow Wave Induction by Propofol to Eliminate Depression (SWIPED) clinical trial. The trial is potentially renewable for up to 4 years and will leverage propofol to determine whether enhancing slow-wave sleep (SWS) is a therapeutic option for alleviating treatment-resistant depression (TRD) and cognitive dysfunction in older adults.

“Disrupted slow-wave sleep is at the nexus of depression and cognitive dysfunction in older adults,” says Palanca, principal investigator for the SWIPED trial. “Slow-wave sleep allows the brain to clear out the garbage; it is restorative for the mind and body.”

The clinical trial will consist of two phases. The study employs a combination of wireless at-home sleep and high-density electroencephalographic (EEG) recordings. The Phase I, proof-of-concept study will monitor 15 individuals as they receive two personalized infusions of propofol tailored for maximal safe induction of EEG slow waves during sedation. Overnight EEG recordings will be acquired by participants before and after infusions to gauge changes in slow-wave sleep. This phase will determine if propofol both induces slow waves during the infusion session and promotes SWS on subsequent nights.

“This study may offer a new way to treat depressed older adults, which helps their sleep, depression, and cognitive function,” says Lenze.

Phase II of the clinical trial will enroll 70 additional patients. Patients will be randomized to two groups: one will be administered propofol to maximize slow waves and the second group will be sedated with propofol but at doses inadequate to induce slow waves. The multidisciplinary team, led by Drs. Palanca and Lenze, will examine short and long-term changes in post-infusion SWS as well as executive function, alertness, and depressive symptoms. This phase will test whether enhancement of SWS leads to improvements in cognitive function and mood.

“This work will enhance our understanding of core deficits contributing to poor mood and cognition in a population at risk for Alzheimer’s disease and related dementias,” says Palanca. “With the rise in the aging population, we hope to provide translatable biomarkers and approaches for future precision medicine, with a long-term goal of improving public health and quality of life for those afflicted with TRD.”

SWIPED Collaborators: ShiNung Ching, Nuri Farber, Brendan Lucey, Chip Reynolds, S. Kendall Smith.

Interested in learning more? Visit the Sleepy Brain Lab and the Healthy Mind Lab.