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Electrical Stimulation in Patients With Unipolar Major Depression (TREND2)

Primary Purpose

Depression

Status
Completed
Phase
Phase 2
Locations
Brazil
Study Type
Interventional
Intervention
Stimulation of the trigeminal nerve (active stimulation)
Placebo stimulation of the trigeminal nerve (placebo)
Sponsored by
Hospital do Coracao
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Depression focused on measuring Electrodes, Implanted, Electric Stimulation Therapy

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Outpatients with non-psychotic, unipolar Major Depressive Disorder assessed via the MINI structured interview and legally capacitated to sign the informed consent for participation in the study;
  • A score of ≥ 14 on the HAM-D17 with Item 1 (depressed mood) ≥ 2;
  • A history of treatment failure with at least 3 adequate trials antidepressants over the previous 6 weeks and less than 6 medications, with no change in antidepressant medication or dose within the previous 6 weeks, and ongoing use of at least one antidepressant (which will continue during participation in the study);
  • Patients with suicidal ideation are eligible only if the thoughts of death or of life not being worth living are not accompanied by a plan or intention for self-harm and lack of self-harming attempt in the past 6 months;
  • Patients with appropriate support to be compliant with the study protocol.

Exclusion Criteria:

  • Patient is mentally or legally incapacitated, unable to give informed consent;
  • Patients with psychosis (psychotic depression, schizophrenia, or schizoaffective diagnoses (lifetime); bipolar disorder (lifetime); dementia (lifetime); delirium or any substance abuse disorder within the past 6 months; eating disorder within the past year; obsessive-compulsive disorder (lifetime); post-traumatic stress disorder within the past year; acute risk for suicide or self-injurious behavior. Patients with diagnostic uncertainty or ambiguity (e.g. rule-out pseudo-dementia of depression) will be excluded;
  • Patients currently receiving more than six medications for treatment of MDD;
  • Patients with exposure to ECT or rTMS or any investigational treatment (for any disorder) within the past 6 months;
  • Prior VNS and/or DBS therapy (lifetime);
  • Past history of skull fracture; cranial surgery entering the calvarium; space occupying intracranial lesion; stroke, CVA, or TIAs; cerebral aneurysm; Parkinson's or Huntington's disease; or Multiple Sclerosis.
  • Current pregnancy, breast feeding, plans to become pregnant during the study, or not using a medically accepted means of contraception;
  • Other medical conditions that would increase the risk of infection or surgical related morbidity and/or would affect compliance with the study protocol.

Sites / Locations

  • Hospital do Coracao

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Stimulation

Placebo Stimulation

Arm Description

Patients assigned to active stimulation arm will receive electrical stimulation during the study.

Patients assigned to the placebo arm did not receive stimulation electrical stimulation for 24 weeks. After this period the participants randomized to sham stimulation will be moved to the active stimulation and will be followed until study completion.

Outcomes

Primary Outcome Measures

Identify a efficacy of eTNS of the V1 branch of the trigeminal nerve
We will use the Hamilton Rating Scale for Depression (HRSD) 17 scores as the main outcome measure to assess the efficacy of sTNS of the V1 branch of the trigeminal nerve as adjunctive treatment for MDD.

Secondary Outcome Measures

Identify the tolerability of eTNS stimulation
Tolerability will be evaluated by the records of adverse effects observed during the randomized, open stimulation. We will apply the Ugvalg for Kliniske Undersgelser (UKU) scale at all visits for all patients and to compare scores between groups. Adverse events will be categorized using the MedDRA Medical Dictionary for Regulatory Activities. Complications reported by active and sham stimulation groups will be compared. The complication risk will be calculated based on the overall study duration.
Identify the long-term recurrence rate of eTNS therapy
We will calculate the recurrence rate of all participants at the end of the open label prospective follow-up. Recurrence is defined as return of HAM-17 scores equal to or superior to the original, after the patient has lodged during partial response (20% decrease of the initial score) or complete response (50% decrease of the initial score).
Identify the duration of the placebo effect
To evaluate the duration of the placebo effect in participants randomized to sham stimulation during the initial 12 weeks of the trial. The mean, median and the standard deviation of the interval time to recurrence will be calculated on placebo stimulation.

Full Information

First Posted
August 21, 2014
Last Updated
September 28, 2016
Sponsor
Hospital do Coracao
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1. Study Identification

Unique Protocol Identification Number
NCT02239822
Brief Title
Electrical Stimulation in Patients With Unipolar Major Depression
Acronym
TREND2
Official Title
Double Blinded Randomized Trial of eTNS as Adjuvant Treatment for Major Unipolar Depressive Disorder.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2016
Overall Recruitment Status
Completed
Study Start Date
December 2013 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospital do Coracao

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Double Blinded Randomized Trial of eTNS as adjuvant treatment for Major Unipolar Depressive Disorder. The primary objective is to assess the safety and tolerability of eTNS (external trigeminal nerve stimulation) of the V1 branch of the trigeminal nerve as an adjunctive treatment for adult patients with the diagnosis of unipolar MDD (Major Depressive Disorder).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depression
Keywords
Electrodes, Implanted, Electric Stimulation Therapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
50 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Active Stimulation
Arm Type
Active Comparator
Arm Description
Patients assigned to active stimulation arm will receive electrical stimulation during the study.
Arm Title
Placebo Stimulation
Arm Type
Placebo Comparator
Arm Description
Patients assigned to the placebo arm did not receive stimulation electrical stimulation for 24 weeks. After this period the participants randomized to sham stimulation will be moved to the active stimulation and will be followed until study completion.
Intervention Type
Procedure
Intervention Name(s)
Stimulation of the trigeminal nerve (active stimulation)
Other Intervention Name(s)
Electrical Stimulation
Intervention Description
Participants will be randomized to active vs. sham stimulation during a period of 24 weeks with a one-way cross over at 12 weeks. After 12 weeks, the participants receiving active electrical stimulation will continue under active stimulation until completion of the study. Participants randomized to sham stimulation will be shifted to active stimulation and will be followed-up until completion of the study. The study will be unblinded after 6 months of randomized stimulation. The second part of the study will be an open label prospective trial for evaluate long-term follow-up. The duration of the open label trial will be more 24 weeks. the duration of the open label trial will be more 24 weeks.
Intervention Type
Procedure
Intervention Name(s)
Placebo stimulation of the trigeminal nerve (placebo)
Other Intervention Name(s)
Sham Eletrical Stimulation
Intervention Description
Participants will be randomized to active vs. sham stimulation during a period of 24 weeks with a one-way cross over at 12 weeks. After 12 weeks, the participants receiving active electrical stimulation will continue under active stimulation until completion of the study. Participants randomized to sham stimulation will be shifted to active stimulation and will be followed-up until completion of the study. The study will be unblinded after 6 months of randomized stimulation. The second part of the study will be an open label prospective trial for evaluate long-term follow-up. The duration of the open label trial will be more 24 weeks.
Primary Outcome Measure Information:
Title
Identify a efficacy of eTNS of the V1 branch of the trigeminal nerve
Description
We will use the Hamilton Rating Scale for Depression (HRSD) 17 scores as the main outcome measure to assess the efficacy of sTNS of the V1 branch of the trigeminal nerve as adjunctive treatment for MDD.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
Identify the tolerability of eTNS stimulation
Description
Tolerability will be evaluated by the records of adverse effects observed during the randomized, open stimulation. We will apply the Ugvalg for Kliniske Undersgelser (UKU) scale at all visits for all patients and to compare scores between groups. Adverse events will be categorized using the MedDRA Medical Dictionary for Regulatory Activities. Complications reported by active and sham stimulation groups will be compared. The complication risk will be calculated based on the overall study duration.
Time Frame
48 weeks
Title
Identify the long-term recurrence rate of eTNS therapy
Description
We will calculate the recurrence rate of all participants at the end of the open label prospective follow-up. Recurrence is defined as return of HAM-17 scores equal to or superior to the original, after the patient has lodged during partial response (20% decrease of the initial score) or complete response (50% decrease of the initial score).
Time Frame
48 weeks
Title
Identify the duration of the placebo effect
Description
To evaluate the duration of the placebo effect in participants randomized to sham stimulation during the initial 12 weeks of the trial. The mean, median and the standard deviation of the interval time to recurrence will be calculated on placebo stimulation.
Time Frame
48 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Outpatients with non-psychotic, unipolar Major Depressive Disorder assessed via the MINI structured interview and legally capacitated to sign the informed consent for participation in the study; A score of ≥ 14 on the HAM-D17 with Item 1 (depressed mood) ≥ 2; A history of treatment failure with at least 3 adequate trials antidepressants over the previous 6 weeks and less than 6 medications, with no change in antidepressant medication or dose within the previous 6 weeks, and ongoing use of at least one antidepressant (which will continue during participation in the study); Patients with suicidal ideation are eligible only if the thoughts of death or of life not being worth living are not accompanied by a plan or intention for self-harm and lack of self-harming attempt in the past 6 months; Patients with appropriate support to be compliant with the study protocol. Exclusion Criteria: Patient is mentally or legally incapacitated, unable to give informed consent; Patients with psychosis (psychotic depression, schizophrenia, or schizoaffective diagnoses (lifetime); bipolar disorder (lifetime); dementia (lifetime); delirium or any substance abuse disorder within the past 6 months; eating disorder within the past year; obsessive-compulsive disorder (lifetime); post-traumatic stress disorder within the past year; acute risk for suicide or self-injurious behavior. Patients with diagnostic uncertainty or ambiguity (e.g. rule-out pseudo-dementia of depression) will be excluded; Patients currently receiving more than six medications for treatment of MDD; Patients with exposure to ECT or rTMS or any investigational treatment (for any disorder) within the past 6 months; Prior VNS and/or DBS therapy (lifetime); Past history of skull fracture; cranial surgery entering the calvarium; space occupying intracranial lesion; stroke, CVA, or TIAs; cerebral aneurysm; Parkinson's or Huntington's disease; or Multiple Sclerosis. Current pregnancy, breast feeding, plans to become pregnant during the study, or not using a medically accepted means of contraception; Other medical conditions that would increase the risk of infection or surgical related morbidity and/or would affect compliance with the study protocol.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alessandra Gorgulho, MD, MSc
Organizational Affiliation
HOSPITAL DO CORAÇÃO
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Antonio De Salles, M.D., Ph.D.
Organizational Affiliation
HOSPITAL DO CORAÇÃO
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Otavio Berwanger, MD,PhD
Organizational Affiliation
HOSPITAL DO CORAÇÃO
Official's Role
Study Director
Facility Information:
Facility Name
Hospital do Coracao
City
São Paulo
State/Province
SP
ZIP/Postal Code
04005-000
Country
Brazil

12. IPD Sharing Statement

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Electrical Stimulation in Patients With Unipolar Major Depression

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