Tractography Guided Subcallosal Cingulate Deep Brain Stimulation for Treatment Resistant Depression

NCT03952962 | Recruiting FDA Device

• 1 other identifier: 19-000767; STU-2021-0635
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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.

Conditions

Treatment Resistant Depression; Undergoing Deep Brain Stimulation (DBS) Surgery

Outcome Measures

Primary Outcomes (1)

• Change in Montgomery and Asberg Depression Rating Scale (MADRS) score.

  The primary endpoint will be defined as at least a 40% reduction in the Montgomery and Asberg Depression Rating Scale (MADRS) that measures depression severity. The MADRS scores range from 0 to 60, where increased values indicate more severe depression. There are 10 questions that each yield a score of 0-6 that are then summed for a total score.

  18 months

Secondary Outcomes (19)

• Change in another related clinical assessment: PHQ-9

  18 months

• Change in another related clinical assessment: QIDS-SR

  18 months

• Change in another related clinical assessment: HAM-A

  18 months

• Change in another related clinical assessment: CSSRS

  18 months

• Change in another related clinical assessment: HAMD-17

  18 months

Study Arms (2)

Randomized Discontinuation Period: OFF then ON DBS

EXPERIMENTAL

Subjects randomized to this arm are initially "OFF" DBS after the open label period then gradually decreased in their optimized setting's amplitude for 8 weeks and then "ON" DBS for 8 weeks.

Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system

Randomized Discontinuation Period: ON then OFF DBS

EXPERIMENTAL

Subjects randomized to this arm are initially "ON" DBS with optimized stimulation settings for 8 weeks after the open label period and then "OFF" DBS with gradually decreasing amplitude for 8 weeks.

Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system

Interventions

Abbott Laboratories Infinity™ implantable deep brain stimulation system DEVICE

Deep brain stimulation (DBS) refers to the process of delivering an electrical current to a precise location in the brain.

Randomized Discontinuation Period: OFF then ON DBS; Randomized Discontinuation Period: ON then OFF DBS

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;
• Pregnant or has plans to become pregnant in the next 36 months;
• 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;

Sponsors & Collaborators

• Nader Pouratian: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Nader Pouratian, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nader Pouratian, MD, PhD

CONTACT

310/274-2095; Nader.Pouratian@UTSouthwestern.edu

Nadia Imran

CONTACT

214/648-7585; Nadia.Imran@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The investigators propose a clinical trial involving 12-months open-label bilateral DBS that targets SCC (using TOT) in subjects with TRD. The open label period is intended to ensure that maximal benefit can be achieved with the current proposed protocol. Following open label optimization, to control for possible placebo, each subject will enter a double blinded randomized discontinuation, intended to confirm clinical benefit of DBS among responders (6 months).
• Purpose: DEVICE FEASIBILITY
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PROFESSOR & CHAIR

Model Details: 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.

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 16, 2019
• Study Start: October 28, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027
• Last Updated: July 2, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)