NCT07050355

Brief Summary

Investigators primary aim is to carry out a two-site, randomized, double-blind, sham-controlled, phase II trial to systematically examine the potential for aerobic exercise (AEx) to enhance the anti-depressant benefits of rTMS in individuals with post-stroke depression (PSD). Investigators propose to determine the efficacy of combining two known anti-depressant treatments shown to be effective in non-stroke depression, aerobic exercise (AEx) and repetitive transcranial magnetic stimulation (rTMS), on post-stroke depressive symptoms. This project is based on the idea that depression negatively affects the potential for the brain to adapt in response to treatment such that rehabilitation may not produce the same changes that it does in non-depressed individuals. Investigators believe that effective treatment for PSD will result in a virtuous cycle whereby reducing depression enhances response to rehabilitation, thereby facilitating functional gains. That is, effectively treating depression will enable individuals to better recover from stroke.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
96

participants targeted

Target at P75+ for not_applicable stroke

Timeline
41mo left

Started Nov 2024

Longer than P75 for not_applicable stroke

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress31%
Nov 2024Aug 2029

Study Start

First participant enrolled

November 1, 2024

Completed
5 months until next milestone

First Submitted

Initial submission to the registry

April 3, 2025

Completed
3 months until next milestone

First Posted

Study publicly available on registry

July 3, 2025

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

August 31, 2029

Last Updated

July 14, 2025

Status Verified

June 1, 2025

Enrollment Period

4.8 years

First QC Date

April 3, 2025

Last Update Submit

July 9, 2025

Conditions

StrokeDepression - Major Depressive DisorderWalking Impairment

Keywords

strokerehabilitationneuromodulationTMSwalkingexercise

Outcome Measures

Primary Outcomes (1)

  • Severity of depressive symptoms

    The Hamilton Depression Rating Scale (HAM-D17) is the gold-standard for clinical trial outcomes and samples a broad array of depressive symptoms. Critically, the rater administering the HAM-D17 will be clinically trained and will blinded to all other aspects of the study. For this trial, depression severity will be classified as moderate (HAM-D17 = 14-19) or severe (HAM-D = 20-25) for the purpose of stratification and diagnosed upon enrollment using the Structured Clinical Interview for Depression according to the Diagnostic \& Statistical Manual of Mental Disorders, 5th Edition (DSM-V).

    baseline, after 2,4,6,8,10 and 12 weeks of treatment

Secondary Outcomes (3)

  • six-minute walk test

    baseline, after 2,4,6,8,10 and 12 weeks of treatment

  • Step activity monitoring

    baseline, after 2,4,6,8,10 and 12 weeks of treatment

  • Stroke Impact Scale

    baseline, after 2,4,6,8,10 and 12 weeks of treatment

Study Arms (3)

rTMS

ACTIVE COMPARATOR

repetitive transcranial magnetic stimulation

Device: rTMS

AEx

ACTIVE COMPARATOR

treadmill aerobic exercise

Behavioral: AEx

rTMS + AEx

EXPERIMENTAL

combination of repetitive transcranial magnetic stimulation and treadmill aerobic exercise

Device: rTMSBehavioral: AEx

Interventions

rTMSDEVICE

Subjects will undergo rTMS to the left dorsolateral prefrontal region as a treatment for depression. Treatment will be performed three times per week for 12 weeks (36 sessions) . We will use a standard resting motor threshold (rMT) determination from unaffected abductor pollicis brevis. Treatments will be delivered at the EEG coordinate for F3 (approximating the left DLPFC) and will be found using the Beam-F3 method. A total of 5000 pulses/session will be delivered at 10Hz with an intensity of 120% of rMT.

rTMSrTMS + AEx
AExBEHAVIORAL

The goal of AEx will be 20 minutes of continuous walking at an intensity of \~70% of heart rate reserve (HRR calculated via the Karvonen method). The desired intensity will be achieved by a combination of increasing treadmill speed and incline. Rest breaks will be allowed as needed during training with the goal of progressing to 20 minutes of continuous walking.

AExrTMS + AEx

Eligibility Criteria

Age21 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • age 21-70
  • stroke within the past 12 to 60 months
  • screen positive for probable major depressive disorder (PHQ-9 \> 10) and HAM-D17 ≥ 14
  • residual paresis in the lower extremity (Fugl-Meyer LE motor score \<34)
  • ability to walk without assistance and without an AFO at speeds ranging from 0.2-1.0 m/s
  • not currently on antidepressant medications or no changes in antidepressant dosage in the last 4 weeks and clinically stable
  • HAM-D17 question #9 regarding suicide \<2
  • provision of informed consent.

You may not qualify if:

  • unable to ambulate at least 150 feet prior to stroke, or experienced intermittent claudication while walking
  • history of congestive heart failure, unstable cardiac arrhythmias, hypertrophic cardiomyopathy, severe aortic stenosis, angina or dyspnea at rest or during ADL's
  • history of COPD or oxygen dependence
  • history of traumatic brain injury
  • blindness or severe visual impairment
  • history of psychosis or other Axis I disorder that is primary
  • life expectancy \<1 yr.
  • severe arthritis or problems that limit participation in testing or training
  • history of DVT or pulmonary embolism within 6 months
  • uncontrolled diabetes with recent weight loss, diabetic coma, or frequent insulin reactions
  • severe hypertension with systolic \>200 mmHg and diastolic \>110 mmHg at rest
  • attempt of suicide in the last 2 years or suicidal risk assessed by SCID
  • history of seizures or currently prescribed anti-seizure medications
  • current enrollment in a trial to enhance motor recovery
  • currently participating in behavioral treatment for depression
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Duke University School of Medicine

Durham, North Carolina, 27710, United States

ACTIVE NOT RECRUITING

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

MeSH Terms

Conditions

StrokeMotor Activity

Condition Hierarchy (Ancestors)

Cerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesBehavior

Central Study Contacts

Chris Gregory, PhD

CONTACT

(843)792-1078gregoryc@musc.edu

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
Outcome assessors will be blinded to group assignment
Purpose
TREATMENT
Intervention Model
FACTORIAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor-Faculty

Study Record Dates

First Submitted

April 3, 2025

First Posted

July 3, 2025

Study Start

November 1, 2024

Primary Completion (Estimated)

August 31, 2029

Study Completion (Estimated)

August 31, 2029

Last Updated

July 14, 2025

Record last verified: 2025-06

Locations

US(2)