Deep Brain Stimulation to Relieve Depression

NCT02889250 | Withdrawn Phase 3 DMC FDA Device

• 1 other identifier: PRO16050040
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open label study with a sample size of 6 to develop deep brain stimulation of the subcallosal cingulate white matter(SCCWM) for late life depression using an experimental medicine approach in which the investigators will program the device based both on 1) a neurophysiologic measure of target engagement and 2) safety (defined as lack of neuropsychiatric worsening and stable neurocognition).

Conditions

Treatment Resistant Depression

Keywords

geriatric; depression; deep brain stimulation; subcallosal cingulate

Outcome Measures

Primary Outcomes (4)

• Theta cordance, measured by magnetoencephalography.

  Theta cordance combines complementary information from absolute (the amount of power in the theta oscillatory band and relative power (the percentage of power contained in the theta band relative to the total spectrum) of EEG spectra.

  6 months

• Symptoms of Depression

  A measure of safety is that the stimulation does not worsen depression. Significant worsening of depressive symptoms is defined as \>/= 30% worsening of symptoms, as measured with the Montgomery Asberg Depression Rating Scale (MADRS) for four consecutive weeks, compared to the average score of the 4 weeks pre-stimulation.

  6 months

• Suicidality

  A measure of safety is that the stimulation does not worsen or cause suicidal ideation or behavior. The Columbia Suicide Severity Rating Scale will assess suicidality. Clinically significant suicidality is defined as greater than 3 on suicidal ideation subscale of the Columbia Suicide Severity Scale AND worsening of the score compared to baseline, OR any suicidal behavior noted on the suicidal behavior subscale.

  6 months

• Neurocognitive status

  A measure of safety is that the stimulation does not worsen neurocognition. The investigators will use a comprehensive validated battery of neuropsychiatric tests to monitor change in memory, executive functioning, psychomotor speed, verbal ability and global cognitive functioning. Clinically significant worsening is defined as deterioration of \> 1 SD in at least two cognitive domains after six months of stimulation, compared to pre-surgical testing.

  6 months

Study Arms (1)

Open Label DBS

EXPERIMENTAL

6 months of DBS

Device: Medtronic Activa SC DBS, Lead Model 3387

Interventions

Medtronic Activa SC DBS, Lead Model 3387 DEVICE

Deep Brain Stimulation

Open Label DBS

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has signed and dated the Screening Consent Form prior to conducting any study-related screening testing
• Following successful completion of the screening phase, subject has signed and dated the Study Informed Consent Form prior to the initiation of any study-related procedures (other than screening testing).
• Subject has been medically cleared for DBS neurosurgical procedure by their primary care doctor and study neurosurgeon.
• Age \>/= 60 years old.
• Subject is fluent in English (written and verbal).
• Subject meets Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnostic criteria for major depressive disorder (MDD) based on Structured Clinical Interview for DSM-5 Axis I Disorders (SCID-I) conducted during the screening testing for the project.
• Subject has medical record documentation that the current major depressive episode (MDE) has persisted for \> 2 years with the exception of brief responses (e.g., \< 8 weeks) to treatments.
• Subject's depression is treatment resistant; the subject has not clinical responded to 4 or more adequate drug trials of therapy for depression as scored by the antidepressant treatment history form.
• Three of the 4 trials need to have occurred in the current depressive episode.
• One of the 4 trials must have included a combination of 2 or more antidepressant medications from 2 different antidepressant classes.
• One of the 4 trials must have included 1 of the following: augmentation agents: lithium, triiodothyronine, buspirone, bupropion, or atypical antipsychotic.
• Subject must have tried a course of ECT.
• Subject's antidepressant medication regimen has been held stable for \> 30 days prior to the study screening MADRS.
• Subject's screening MADRS score \> 25.
• Average pre-operative MADRS score of 25 or greater (averaged over at least four weekly pre-surgical evaluations during the weeks prior to surgery) .

You may not qualify if:

• Inability to provide informed consent.
• Inability to tolerate general anesthesia.
• Subject has been hospitalized for treatment of depression \< 30 days prior to the screening testing.
• Active suicidal ideation with intent, suicide attempt within the last six months, or more than three suicide attempts within the last two years. Urgent psychiatric referral will be made in these cases.
• Subject made a suicide attempt requiring medical treatment \< 3 months prior to the screening testing.
• Subject has a history of 2 or more suicide attempts \< 12 months prior to the screening testing.
• Subject poses an imminent suicide risk in the opinion of the investigator.
• Subject is currently enrolled in or plans to enroll in any concurrent drug and/or device study that may confound the results of this study.
• Subject has a history of a seizure disorder.
• Subject will be exposed to diathermy.
• Subject has a history of a neurosurgical ablation procedure.
• Subject has a life expectancy of \< 3 years.
• Significant cerebrovascular risk factors or history of stroke, major head trauma, neurodegenerative disorder, or other general contraindications for DBS surgery (cardiac pacemaker/defibrillator or other Ferromagnetic implanted devices).
• Contraindication to MRI.
• Dementia, as defined by Modified Mini Mental State Examination (3MS) \< 84 and clinical evidence of dementia. Patients screened out due to possible dementia will be referred to the local Memory Clinic or Alzheimer's Disease Research Center for evaluation to clarify the presence or absence of dementia.

Sponsors & Collaborators

• Jordan F. Karp: lead

Related Links

• Richardson RM, Ghuman AS, Karp JF. Results of the First Randomized Controlled Trial of Deep Brain Stimulation in Treatment-Resistant Depression. Neurosurgery. 2015 Aug;77(2):N23-4.
• Alhourani A, McDowell MM, Randazzo MJ, Wozny TA, Kondylis ED, Lipski WJ, Beck S, Karp JF, Ghuman AS, Richardson RM. Network effects of deep brain stimulation. J Neurophysiol. 2015 Oct;114(4):2105-17.

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: August 13, 2016
• First Posted: September 5, 2016
• Study Start: June 1, 2018
• Primary Completion: December 1, 2019
• Study Completion: March 1, 2020
• Last Updated: August 6, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share