Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

DBS of the Lateral Habenula in Treatment-Resistant Depression

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01798407
Recruitment Status : Recruiting
First Posted : February 25, 2013
Last Update Posted : January 16, 2019
Sponsor:
Information provided by (Responsible Party):
Wayne Goodman MD, Baylor College of Medicine

Brief Summary:
This research study will investigate the safety, tolerability, and benefit of bilateral deep brain stimulation (DBS) to the lateral habenula in subjects with treatment-resistant major depression (TRD) secondary to either nonpsychotic unipolar major depressive disorder (MDD), or bipolar disorder (BD) I. Six adult subjects with TRD will be treated in this single-site study at Baylor College of Medicine; subjects will be chronically symptomatic with significant functional disability, and will have demonstrated resistance to standard somatic and pharmacotherapeutic treatments. The primary outcome measure will be the change in the 17-item Hamilton Depression Rating Scale (HDRS^17) six months after the commencement of stimulation.

Condition or disease Intervention/treatment Phase
Treatment Resistant Major Depressive Disorder Device: Activa Tremor Control Sys (DBS Implant) Other: Randomized, staggered withdrawal phase Not Applicable

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: all subjects will receive bilateral surgical implantation of DBS system. Those who respond at 12 months will enter a randomized, staggered withdrawal phase. See masking description below.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: During staggered withdrawal phase, double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen every 2 weeks until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.
Primary Purpose: Treatment
Official Title: A Clinical Pilot Study Examining Bilateral Inhibition of the Lateral Habenula as a Target for Deep Brain Stimulation in Intractable Depression
Actual Study Start Date : February 2013
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : February 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Activa Tremor Control Sys (DBS Implant)
all subjects will receive bilateral surgical implantation of DBS system. Those who respond at 12 months will enter a randomized, staggered withdrawal phase.
Device: Activa Tremor Control Sys (DBS Implant)
DBS system consists of the Activa RC 37612 System (Implantable Pulse Generator with Model 37085 Extensions (40 to 95cm), Activa Patient Programmer, and Medtronic Model 3389 DBS Lead). This system is commercially approved for the treatment of chronic, intractable Parkinson's Disease. It will be used with the Model SP-10344 Memory Mod Software which enables the physician to program the Implantable Pulse Generator to a higher frequency.
Other Names:
  • Deep Brain Stimulation System
  • DBS
  • Activa RC System

Experimental: Randomized, staggered withdrawal phase
For responders only: double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen biweekly until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.
Other: Randomized, staggered withdrawal phase
For responders only: double blind discontinuation will be attempted on either the 12 or 13 month visit. Stimulation intensity will be decreased by 50% and then completely discontinued two weeks later. Subjects will be seen biweekly until 15 months post activation or escape criteria are met. These escape criteria include relapse at 2 visits, hospitalization, active suicidal ideation, or withdrawing consent. If any of these criteria are met, the blind will be broken and open treatment will be resumed.




Primary Outcome Measures :
  1. Change in HDRS^17 score from baseline to 6 months after the commencement of stimulation [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    'Response' is categorically defined as a ≥ 50% reduction in the HDRS17 score relative to the baseline assessment. 'Remission' is defined as an absolute HDRS17 score < 8. Study success criteria will be defined as ≥ 3 of the 6 patients meeting the individual subject success criteria of response or remission by HDRS17 score at the 6 month time point.


Secondary Outcome Measures :
  1. MADRS (Montgomery and Asberg Depression Rating Scale) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Clinician administered evaluation of depressive symptoms

  2. Clinical Global Impression of Severity (CGI-S) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Clinician Administered assessment

  3. Clinical Global Impression of Improvement (CGI-I) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Clinician administered assessment

  4. Young Mania Rating Scale (YMRS) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Clinician administered assessment

  5. Columbia Suicide Severity Rating Scale (C-SSRS) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Clinician administered assessment

  6. Neuropsychological Battery [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Clinician administered assessment includes WAIS-IV subscales subscales: Digit Span, Information, Coding, Similarities, and Visual Puzzles; TMT (Trail Making Tests) A and B; Neuropsychological Assessment Battery (NAB): Naming Test; JLO, (Benton Judgment of Line Orientation Test [Forms H and V]); HVLT-R (Hopkins Verbal Learning Test-R [Forms 1, 2, 3, and 4]); BVMT-R (Brief Visual Spatial Memory Test, Revised [Forms 1, 2, 3, and 4]); GPT (Grooved Pegboard Test); COWAT (Controlled Oral Word Association Test) with semantic fluency; WCST (Wisconsin Card Sorting Test) - short version (64 item); Stroop (Stroop Color Word Test); IGT(Iowa Gambling Task)

  7. QIDS-SR (Quick Inventory of Depressive Symptomatology) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Subject self rated assessment

  8. Generalized Anxiety Disorder 7-item Scale (GAD-7) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Subject self rated assessment

  9. Sheehan Disability Scale [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Subject self rated assessment

  10. PRISE (The Patient Rated Inventory of Side Effects) [ Time Frame: baseline, Month 6, Month 12 and 18 months ]
    Subject self report of adverse events (and collection)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men and women (non-pregnant) between ages 21 and 70;
  • DSM-5 diagnosis (assessed by Structured Clinical Interview for DSM-5, SCID-5) of a current major depressive episode (MDE), recurrent or single episode with first episode before age 45, secondary to either nonpsychotic unipolar major depressive disorder (MDD)or bipolar disorder (BD) I;
  • Chronic illness with current MDE ≥ 24 months duration and/or recurrent illness with at least a total of 4 lifetime episodes (including current episode ≥ 12 months);
  • For subjects with a bipolar disorder: the last manic or hypomanic episode must have been ≥ 24 months before study enrollment and patients must be maintained on a mood stabilizer (e.g. lithium or another mood stabilizer approved for bipolar disorder).
  • Treatment resistance (defined by criteria on the Antidepressant Treatment History Form): Failure (i.e. persistence of the major depressive episode) to respond to a minimum of three adequate depression treatments from at least two different treatment categories (e.g. SSRI's, TCA's, other antidepressants, lithium-addition, irreversible MAO-inhibitor, antidepressant augmentation with an atypical antipsychotic medication); also, if diagnosed as bipolar, failure to respond to (or inability to tolerate) a minimum of three treatments approved for bipolar disorder, including lithium and at least one medication FDA-approved for bipolar depression (e.g., olanzapine/fluoxetine combination, quetiapine, lurasidone).
  • Previous trial of ECT (lifetime)
  • Symptom Severity: HDRS17 ≥ 21; on two separate assessments (at initial screening and 1 week before surgery), over a 1-month period;
  • Normal brain MRI within 3 months of surgery;
  • Stable antidepressant medical regimen for the month preceding surgery
  • Modified mini-mental state examination (MMSE) score ≥ 27;
  • Normal thyroid stimulating hormone (TSH) level within 12 months of study entry;
  • Other medical conditions must be stable for at least 1 year;
  • Anticipates a stable psychotropic medication regimen in the next 24 months;
  • Subject must be able to identify a family member, physician, or friend who will participate in the Treatment Contract;
  • Able and willing to give informed consent.

Exclusion Criteria:

  • Schizophrenia Spectrum or Other Psychotic Disorders (excluding Schizotypal (Personality) Disorder and Substance/Medication Induced Psychotic Disorder); presence of primary or serious (requiring additional treatment) disorders: comorbid obsessive compulsive disorder, post-traumatic stress disorder, panic disorder, bulimia or anorexia, in the last year;
  • Cluster A or B personality disorder;
  • Alcohol or substance abuse/dependence within 6 months, excluding nicotine and cannabis provided that participant either a) has a legal prescription or b) is a legal resident of a state where recreational cannabis use is legal;
  • Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or had a serious suicide attempt within the last year;
  • Neurological disease that impairs motor, sensory or cognitive function or that requires intermittent or chronic medication (e.g., Parkinson's disease, MS, stroke);
  • Any history of seizure disorder or hemorrhagic stroke;
  • Any medical contraindication to surgery, including infection or coagulopathy;
  • Participation in another drug, device, or biological trial within 30 days;
  • Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators including spinal cord stimulators, and deep brain stimulators;
  • Does not have adequate family/friend support as determined by psychological screening and/or interview;
  • Abnormal brain MRI;
  • Unable to maintain a stable psychotropic medication regimen in the next 24 months
  • Pregnant or has plans to become pregnant in the next 24 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01798407


Contacts
Layout table for location contacts
Contact: Gregory Vogt (713) 798-4729 gsvogt@bcm.edu
Contact: Luke Jumper (713) 798-4113 jumper@bcm.edu

Locations
Layout table for location information
United States, Texas
Baylor College of Medicine Recruiting
Houston, Texas, United States, 77030
Contact: Gregory Vogt    713-798-4729    gsvogt@bcm.edu   
Contact: Luke Jumper    (713) 798-4113    Jumper@bcm.edu   
Principal Investigator: Wayne K Goodman, MD         
Sub-Investigator: Ashwin Viswanathan, MD         
Sub-Investigator: Sanjay Mathew, MD         
Sub-Investigator: Meghan Robinson, PhD         
Sub-Investigator: Joohi Jimenez-Shahed, MD         
Sub-Investigator: Ramiro Salas, PhD         
Sub-Investigator: Stefan Ursu, MD         
Sub-Investigator: Adriana Strutt, PhD         
Sub-Investigator: Sameer Sheth, MD         
Sponsors and Collaborators
Wayne Goodman MD
Investigators
Layout table for investigator information
Principal Investigator: Wayne K Goodman, MD Baylor College of Medicine

Publications:

Layout table for additonal information
Responsible Party: Wayne Goodman MD, Principal Investigator; Chairman, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT01798407     History of Changes
Other Study ID Numbers: H40307
49593 ( Other Identifier: BCM )
277909 ( Other Identifier: Simons Foundation )
HSM#12-00467 ( Other Grant/Funding Number: MSSM IRB )
GCO 12-1815 ( Other Identifier: MSSM IRB )
First Posted: February 25, 2013    Key Record Dates
Last Update Posted: January 16, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Device Product Not Approved or Cleared by U.S. FDA: No
Pediatric Postmarket Surveillance of a Device Product: No

Keywords provided by Wayne Goodman MD, Baylor College of Medicine:
Deep Brain Stimulation
Major Depressive Disorder
Depression
Lateral Habenula
Intractable Depression
Treatment Resistant Depression (TRD)

Additional relevant MeSH terms:
Layout table for MeSH terms
Depression
Depressive Disorder
Depressive Disorder, Major
Depressive Disorder, Treatment-Resistant
Behavioral Symptoms
Mood Disorders
Mental Disorders