Clinical trial NCT03952962: Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression
Official title: Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Treatment Resistant Depression
Undergoing Deep Brain Stimulation (DBS) Surgery
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
First posted: 2019-05-16
Enrollment: 12
Sex: ALL
Minimum age (years): 21
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: There will be an initial 12-month open label period for all participants involved. In the second period of the study, patients will be divided into groups: responders (defined as a 40% reduction or more in MADRS) versus non-responders. Responders will continue to the 6-month double-blinded discontinuation phase (see below for additional details of study procedures during this phase). The non-responders, after the open label period (12 months) will have monthly follow-up visits for 12 mo. During the discontinuation period, patients will be randomized to either the ON or OFF stimulation phase for 3 mo each. If randomized to ON, there will be no change for 3 mo, then a biweekly 25% reduction in stimulation amplitude for the next 3 mo until stimulation is off. If randomization to OFF phase, there will be an initial biweekly 25% reduction in stimulation amplitude for 3 mo until the device is off then the stimulation settings will be turned back to the optimized settings for three months.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: Treatment resistant depression remains a major problem for individuals and society. Surgical procedures may provide relief for some of these patients. The most frequently considered surgical approach is deep brain stimulation (DBS) of a part of the brain called the subcallosal cingulate region. However, the effectiveness and safety is not well established. The investigators will use a novel approach using advanced imaging technique (magnetic resonance tractography) to evaluate the feasibility and safety of this surgical approach. An innovative method for the definition of DBS target will be applied that redefines the concept of targeting as one of targeting a symptomatic network rather than a structural brain region using subject-based brain anatomy to define the target location. The correlation between imaging findings at baseline with the mood score changes at different time points of the study will be investigated.


Eligibility criteria: Inclusion Criteria:

* Men and women (non-pregnant) between ages 21 and 70;
* DSM-5 diagnosis a current major depressive episode (MDE) for 10 years of less, recurrent or single episode with first episode after adulthood and did not start during childhood or adolescence, secondary to nonpsychotic unipolar major depressive disorder;
* Current index MDE ≥24 months duration and/or recurrent illness with at least a total of 2 lifetime episodes (including current episode \>12 months);
* Treatment resistance (defined by criteria on the Antidepressant Treatment History Form (ATHF)28): Failure to respond to a minimum of four adequate depression treatments from different categories;
* Symptom severity for Screening: Hamilton Depression Rating Scale-17 item (HDRS17) ≥20;
* Symptom severity for Outcome: Montgomery Asberg Rating Scale (MADRS) ≥27 to be met at assessment one week pre-op;
* Normal brain MRI within 3 months of surgery;
* Antidepressant medication regimen has been held stable for ≥ 30 days prior to the study screening MADRS;
* Remain on stable antidepressant medication throughout the study, unless there are safety concerns;
* Montreal Cognitive Assessment (MoCA) \>25;
* Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months.

Exclusion Criteria:

* DSM-5 Axis I Disorders: any lifetime history of psychotic disorder or bipolar disorder;
* Alcohol or substance use disorder within 6 months, excluding nicotine;
* History of childhood abuse (physical or sexual) 18
* Personality disorders;
* Seeking disability during the trial;
* Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made any suicide attempt within the last year; (MADRS ≥ 5 including the day of surgery);
* No stable work history;
* Neurological/Medical condition that makes the patient, in the opinion of the surgeon, a poor candidate;

  1. Pregnant or has plans to become pregnant in the next 36 months;
  2. Unable/unable to practice birth control through the period of randomization and withdrawal of therapy;
* Subjects who have a history of a seizure disorder;
* Subjects who will be exposed to diathermy;
* Subjects who have any medical contraindications to undergoing DBS surgery (e.g. infection, coagulopathy, or significant cardiac or other medical risk factors for surgery);
* Subjects with another implanted device such as a cardiac pacemaker, defibrillator or neurostimulator;
* Subjects who have a history of hemorrhagic stroke;
* Subjects who are unable to undergo MRI;
* Subjects who are at increased risk of hemorrhage due to underlying medical conditions or medication.

Primary outcomes:
measure: Change in Montgomery and Asberg Depression Rating Scale (MADRS) score.
timeFrame: 18 months
Secondary outcomes:
measure: Change in another related clinical assessment: PHQ-9
timeFrame: 18 months
measure: Change in another related clinical assessment: QIDS-SR
timeFrame: 18 months
measure: Change in another related clinical assessment: HAM-A
timeFrame: 18 months
measure: Change in another related clinical assessment: CSSRS
timeFrame: 18 months
measure: Change in another related clinical assessment: HAMD-17
timeFrame: 18 months
measure: Change in another related clinical assessment: SCID-II
timeFrame: 18 months
measure: Change in another related clinical assessment: CGI
timeFrame: 18 months
measure: Change in another related clinical assessment: PGI
timeFrame: 18 months
measure: Change in another related clinical assessment: MoCA
timeFrame: 18 months
measure: Change in another related clinical assessment: SAFTEE-SI
timeFrame: 18 months
measure: Change in another related clinical assessment: SF-36
timeFrame: 18 months
measure: Change in another related clinical assessment: QOL
timeFrame: 18 months
measure: Change in another related clinical assessment: HLQ
timeFrame: 18 months
measure: Change in another related clinical assessment: YMRS
timeFrame: 18 months
measure: Change in another related clinical assessment: PSQI
timeFrame: 18 months
measure: Change in another related clinical assessment: ISI
timeFrame: 18 months
measure: Change in another related clinical assessment: LAPS
timeFrame: 18 months
measure: Change in another related clinical assessment: SHAPS
timeFrame: 18 months
measure: Change in another related clinical assessment: TEPS
timeFrame: 18 months
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Nader Pouratian, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: