DBS for Treatment Resistant Depression (CRIO-DBS)

Therapeutic Brain Stimulation for Refractory Depression

The purpose of this study is to examine the effects of sub-callosal cingulate (SCC) deep brain stimulation (DBS) in patients with treatment resistant depression (TRD).

The working hypotheses are that long pulse-width DBS applied to the SCC region will lead to improvements in TRD patients, and specific neuroimaging biomarkers will correlate with response to DBS; the functional recovery will be enhanced with concurrent cognitive behavioural therapy (CBT).

Study Overview

• Status: Completed
• Conditions: Depressive Disorder, Treatment-Resistant
• Intervention / Treatment: Device: deep brain stimulation with short & long pulse width

Detailed Description

The aim is to collect data on prediction, optimization and augmentation of DBS for TRD and develop tools for DBS surgery. It is a biological pilot study designed to provide informative data for future work.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary & Alberta Health Services, Foothills Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age 20-70
• diagnosis of major depressive (MDD)or bipolar disorder(BP)determined independently by 2 study psychiatrists
• current major depressive episode of >1 year duration, treatment-resistant (meaning failure to respond to 4 different classes of antidepressants, including augmentation or combination strategies with lithium, atypical antipsychotics, anticonvulsants, antidepressants, evidence-based psychotherapy, CBT, or electroconvulsive treatment despite adequate dosage, duration and compliance)
• minimum score of 20 (out of 52) on the 17 item Hamilton Depression Rating Scale (HDRS)
• resident of Alberta, Canada, covered by Alberta Health

Exclusion Criteria:

• other Axis I psychiatric disorders including schizophrenia, psychosis, active suicidal ideation over previous 6 months
• cerebrovascular risk factors, previous stroke, head injury and neurodegenerative disorders, pregnancy, medical and general contraindications for DBS surgery (e.g. cardiac pacemaker/defibrillator)
• age >70
• diabetes

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Long Pulse Width; deep brain stimulation with short & long pulse width	Device: deep brain stimulation with short & long pulse width; surgical implantation for bilateral electrodes and stimulation using short and long pulse width
Experimental: Short Pulse Width; deep brain stimulation with short & long pulse width	Device: deep brain stimulation with short & long pulse width; surgical implantation for bilateral electrodes and stimulation using short and long pulse width

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Hamilton Depression Rating Scale	change in HDRS from baseline before surgery: rates of remission (defined as an HDRS score <8 at 6 and 12 months) and response (defined as >50% reduction in HDRS)	6 and 12 months post-operatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline on Illness Density Index, Montgomery-Asberg Depression Rating Scale and Hamilton Anxiety Scale, Positive and Negative Affect Scale, Clinical Global Impression of Change, GAF< SAs, NAS, Q-LES-Q-SF & neuropsychological tests	change in MADRS score from baseline before surgery to 6 and 12 months post operatively	6 and 12 months post operatively
Post Cognitive Behavioural Therapy Scores	Changes in primary and secondary measures from pre-CBT scores will be used	15 months post operatively

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Zelma H Kiss, MD PhDFRCSC, University of Calgary, Department of Clinical Neurosciences; Principal Investigator: Rajamannar Ramasubbu, MD MRCP FRCP, University of Calgary, Department of Psychiatry

Publications and helpful links

General Publications

• Ramasubbu R, Clark DL, Golding S, Dobson KS, Mackie A, Haffenden A, Kiss ZH. Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial. Lancet Psychiatry. 2020 Jan;7(1):29-40. doi: 10.1016/S2215-0366(19)30415-8.

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): December 1, 2017
• Study Completion (Actual): March 1, 2018

Study Registration Dates

• First Submitted: November 7, 2013
• First Submitted That Met QC Criteria: November 7, 2013
• First Posted (Estimate): November 14, 2013

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Major depressive disorder (MDD); Bi-polar disorder (BP)
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
• Other Study ID Numbers: E-20948

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: undecided