Role of Slow-wave Activity and Plasticity in MDD (SWIP)

Investigating the Role of Slow-wave Activity as a Marker of Impaired Plasticity in Major Depressive Disorder

The hypothesis underlying this proposal is that deficits of synaptic plasticity underlie the slow-wave activity (SWA) abnormalities observed n major depressive disorder (MDD), and that manipulating SWA may serve to circumvent these deficits by facilitating an increase in synaptic strength via the inhibition of synaptic down-scaling, thereby improving plasticity and mood.

Study Overview

• Status: Active, not recruiting
• Conditions: Depression
• Intervention / Treatment: Behavioral: slow-wave disruption

Detailed Description

VISIT 1: Screening. Participants who meet initial inclusion criteria via phone screen will be invited to the laboratory for an in-person screening visit that includes additional screening (e.g. Medical history, TMS eligibility, hearing test for SW disruption procedure), and a structured clinical interview to determine final study eligibility. All subjects will receive verbal and written explanation of the general goals and risks of the study and will sign an informed consent. At this session, participants will also have the opportunity to become acquainted with the TMS and SW disruption procedures. In the case that remote visits are being utilized, such as during the COVID-19 pandemic, this will be separated into a virtual visit (consent, clinical interview, etc. - anything that can be conducted remotely will be) and an in-person visit (hearing test, TMS demonstration). Participants will also choose two dates, at least two nights apart and at most separated by two weeks, for the in-lab visits.

At-home Sleep Recording. For 7 days prior to the in-lab study visits, participants will be asked to keep a consistent at-home sleep schedule, based on habitual rise time (e.g., 10:30 PM - 6 AM). Participants will also consent to refraining from napping, using alcohol and drugs, and limiting caffeine use to one caffeinated beverage before noon throughout the study. These procedures will be confirmed using actigraphy, and sleep diary. Actigraphy provides a validated measure of sleep-wake patterns based on light and activity levels utilizing a wrist-watch like device (Actiwatch 2 and Actiwatch Spectrum Pro, Philips Respironics, Inc.). Sleep diaries will be used to document bedtime and rise time, and several other sleep parameters. Participants will also be asked to note if actigraphs were removed, for how long and for what purpose. Sleep diaries will be completed via the REDCap web-based application if participants have consistent Internet access. Paper and pencil versions of sleep diaries will also be available. Study staff will compare across these methods to verify adherence to study guidelines prior to the in-lab study.

VISIT 2: Baseline Night. Visit 2 and Visit 3 occur on two separate days, in a counterbalanced design to ensure no order or learning effects. The following procedure description will occur in half of participants where Visit 2 precedes Visit 3; however identical procedures will be used for the remaining half of participants where Visit 3 will precede Visit 2. Participants will arrive at the Clinical Research Center for Sleep (CRCS) at 8pm on Visit 2. Following their arrival and orientation, EEG electrodes will be applied. Participants sleep will then be monitored overnight. In the morning, participants will have their blood drawn, and after a light breakfast, the HAM-D will be administered, and then participants will be asked to fill out mood questionnaires (BDI, VAS, PANAS, KSS), and complete a battery of tasks including memory tasks, and resting EEG. They will then be accompanied to the Richards Building to complete the TMS protocol, before returning to the CRCS.

VISIT 3: Slow-wave Disruption. Procedures for Visit 3 are identical for those for Visit 2, with the exception of the following: Utilizing real-time EEG monitoring during sleep, left (C3) and right central (C4) channels will be continuously inspected. Whenever two delta waves (14 Hz; 75 V) appear within 15 seconds, an acoustic stimulus (i.e. tone; frequency = 1000 Hz; intensity = 20100 dB) will be administered through a speaker mounted above the bed, beginning with the lowest intensity (20 dB) and increased by 5 dB intervals if no response occurs (sleep stage shift, K complex, EEG desynchronization, mixed and fast frequency, alpha burst, muscle tone increase, slow eye movements). Utilizing this methodology, the type and incidence of tones played will be tailored to each participant to suppress slow waves without arousing the subject. Disruption of SWA will take place without waking the subject or decreasing total sleep time. The selective SW disruption procedure has been described in detail elsewhere.

TMS The TMS system is housed in the Richards Biomedical Building. Only individuals trained by the IDE sponsor (Desmond Oathes, Ph.D.) and Center Director (Yvette Sheline, M.D.) will dispense TMS. Since all TMS procedures are being conducted in Dr. Sheline's lab, all plans for receipt, storage, labelling, dispensing, returning of failed devices, and destruction will fall under the center's SOPs.

• Study Type: Interventional
• Enrollment (Actual): 76
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Holly Barilla, M.S.; Phone Number: 215-746-4384; Email: holly.barilla@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Department of Psychiatry

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age: 25-50
• Right handed
• English speaking
• Normal cognition
• Normal or corrected-to-normal vision and hearing
• Current depression as assessed on the SCID and Hamilton Rating Scale for Depression
• Stable, normally-time sleep-wake cycles as determined by interview, 1-week daily sleep log and 1-week wrist actigraphy evidence

Exclusion Criteria:

• Current or prior medical condition
• History of stroke, epilepsy, brain aneurysm clip or head injury causing unconsciousness
• Implanted devices (i.e. aneurysm clip or cardiac pacemaker)
• Sleep disorders other than insomnia
• History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders
• No history of depression for the control group.
• For women, pregnancy will exclude participation.
• Lifetime history of electroconvulsive therapy
• travel beyond 2 time zones in the 2 months before study
• Unwillingness to refrain from using alcohol or caffeine during the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subjects with Major Depressive Disorder; Subjects who get assigned to this group will undergo a Diagnostic and Statistical Manual for Mental Disorders (SCID) assessment to determine is they meet criteria for MDD.	Behavioral: slow-wave disruption; A tone will be played through a speaker mounted over the bed that disrupts subjects while they are in slow-wave sleep. The tone will not be loud enough to wake up.
Active Comparator: Control; Subjects who get assigned to this group will undergo a Diagnostic and Statistical Manual for Mental Disorders (SCID) assessment to determine they do not meet criteria for MDD.	Behavioral: slow-wave disruption; A tone will be played through a speaker mounted over the bed that disrupts subjects while they are in slow-wave sleep. The tone will not be loud enough to wake up.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare indices of net synaptic strength (theta power, transcranial magnetic stimulation evoked potentials) and markers associated with plasticity (BDNF, behavioral measures of learning/memory) in individuals with MDD to healthy controls	Waking EEG Theta power - Brain rhythm assessed during waking used to measure net synaptic strength	up to a month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine if slow-wave disruption alters mood in individuals with MDD	Hamilton rating scale for depression - Clinician-administered measure of depression severity	up to a month

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Jennifer Goldschmied, PhD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2020
• Primary Completion (Actual): March 31, 2023
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: October 7, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 5, 2019

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 832986

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: All subject data will be de-identified.

Drug and device information, study documents

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