Spinal Cord Stimulation for the Treatment of Major Depressive Disorder

Study Overview
=================
Brief Summary
-----------------
This pilot clinical trial will evaluate the efficacy and safety of transcutaneous direct current stimulation (tsDCS) in major depressive disorder.

Detailed Description
-----------------
This study aims to 1) determine the efficacy and safety of tsDCS in adult patients with MDD and 2) investigate interoceptive awareness, somatic symptoms, autonomic and metabolic regulation as potential mediators of antidepressant response to tsDCS. We predict that 1) Active tsDCS treatment will result in a greater decrease in depressive symptom severity compared to Sham tsDCS in adult patients with MDD, 2) active tsDCS will be safe and well tolerated in adult patients with MDD and 3) change in interoceptive awareness, somatic symptoms, and autonomic and metabolic parameters will be associated with change in depressive symptom severity. To accomplish these aims, we will conduct an 8-week, double blinded, randomized, sham controlled, parallel group, pilot clinical trial study design. A total of 20 adult antidepressant-free MDD patients will be randomized to receive Active (n=10) or Sham (n=10) tsDCS protocols for 8 weeks in a 1:1 ratio. We will combine the use of a tsDCS device, psychometric instruments to diagnose MDD, and measures of depressive symptom severity, somatic symptoms, interoceptive awareness, autonomic function (blood pressure, heart rate), and potential metabolic markers as predictors of response.

Official Title
-----------------
Spinal Cord Stimulation for the Treatment of Major Depressive Disorder

Conditions
-----------------
Major Depressive Disorder

Intervention / Treatment
-----------------
* Device: Active transcutaneous spinal direct current stimulation
* Device: Sham transcutaneous spinal direct current stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: age 18-55 yrs., inclusive female or male BMI 18.5 to 35 kg/mts2, inclusive current MDD episode diagnoses confirmed by Mini International Neuropsychiatric Interview (MINI) 5.0 with a duration of ≥1 month and ≤24 months moderate MDD symptoms according to Montgomery-Asberg Depression Rating Scale (MADRS) score ≥ 20 to ≤35 no current or recent (past month) antidepressant pharmacological treatment GAD and other anxiety symptoms will be permitted using an effective contraceptive method (all participants of childbearing potential). Exclusion criteria: Current or lifetime MDD episode non-responsive to two or more antidepressant treatments at adequate doses and time (including ECT) Current or lifetime bipolar disorder or schizophrenia diagnosis current (past month): PTSD, psychotic or substance use disorder (nicotine and caffeine allowed) significant risk of suicide according to CSSRS or clinical judgment, or suicidal behavior in the past year current chronic severe pain conditions current chronic use of: opioids analgesics, medications that affect blood pressure or drugs with significant autonomic effects (stimulants and antipsychotics allowed if dose stable for 1 month) neurological, endocrinological, cardiovascular (including diagnosed hypertension) or other clinically significant medical conditions as judged by the clinician skin lesions on electrode placement region implanted electrical medical devices Pregnancy suspected IQ<80 any other clinically relevant reason as judged by the clinician.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 8-week, double blinded, randomized, sham controlled, parallel group, pilot clinical trial study design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Treatment<br>Thoracic anodal transcutaneous spinal direct current stimulation 2.5mA for 20 min/ three times per week for 8 weeks. | Device: Active transcutaneous spinal direct current stimulation<br>* Active anode electrodes placed at Thoracic 10 level, Cathode electrode placed on right shoulder.<br>|
| Sham Comparator: Sham Treatment<br>Thoracic anodal transcutaneous spinal direct current sham stimulation session of 20min/ three times per week for 8 weeks. | Device: Sham transcutaneous spinal direct current stimulation<br>* Sham anode electrodes placed at Thoracic 10 level, Cathode electrode placed on right shoulder.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MADRS score change | Difference in change from baseline to week 8 (or last available observation) in MADRS scores between active and sham tsDCS groups. | 8 weeks (or last available observation). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event frequency difference | Differences in adverse event frequency between active and sham tsDCS groups | 8 weeks | 
| Clinical Global Impression-Severity (CGI-S) | CGI-S change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Clinical Global Impression-Improvement (CGI-I) | CGI-I change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| MADRS Sub-component score | MADRS Sub-Component score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| PHQ-9 score change | PHQ-9 score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Multidimensional Assessment of Interoceptive Awareness (MAIA) score change | MAIA score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Binge Eating Scale (BES) score change | BES score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Four-Dimensional Symptom Questionnaire (4-DSQ) score change | 4-DSQ score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Blood Pressure score change | Blood Pressure score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Heart Rate score change | Heart Rate score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Body Mass Index change | BMI change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Waist Circumference change | Waist Circumference score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Hip Circumference change | Hip Circumference score change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Adiponectin level change | Adiponectin level change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Leptin level change | Leptin level change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Cortisol level change | Cortisol level change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Insulin level change | Insulinl level change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| FGF-21 level change | FGF-21 level change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 
| Fatty Acid (LCn-3) level change | Fatty Acid (LCn-3) level change from baseline to week 8 (or last available observation) difference between Active and Sham tsDCS groups. | 8 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
depression, transcutaneous spinal direct current stimulation, non-invasive, major depressive disorder