European Deep Brain Stimulation (DBS) Depression Study

A Clinical Evaluation of Different Device Parameters for the Management of Patients With Treatment Resistant Major Depressive Disorder, Single or Recurrent Episode, With Deep Brain Stimulation

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01331330

Enrollment

Registered

2011-04-08

Start date

2011-05-31

Completion date

2015-01-31

Last updated

2024-11-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Depressive Disorder, Major

Keywords

Depressive Disorder, Unipolar, Implantable Stimulation Electrodes

Brief summary

To evaluate the effects of two different programming settings of deep brain stimulation (DBS) in the subgenual white matter (Brodmann Area 25 WM) as an adjunctive treatment for treatment resistant Major Depressive Disorder (TR-MDD), single or recurrent episode on mood as measured by the MADRS.

Detailed description

The European Study was a prospective, multicenter, double-blind, randomized study comparing high frequency stimulation (130 Hz) to low frequency stimulation (20 Hz). Subjects underwent 2 baseline evaluations by 2 separate psychiatrists and were implanted with the Libra DBS system. Subjects were randomized to receive either high or low frequency stimulation. The primary endpoint was evaluated after 6 months of stimulation.

Interventions

DEVICEDeep Brain Stimulation

Normal DBS Programming

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

21 Years to 70 Years

Healthy volunteers

Inclusion criteria

* Men and women (non-pregnant) age is 21-70 years; * Diagnosed with non-psychotic major depressive disorder, single or recurrent episode by Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition, Text Revision, 2000 (DSM-IV-TR) criteria derived from the Mini International Neuropsychiatric Interview (MINI); * First episode onset before age 45; * Current episode \> 12 month duration; * In the current episode: Documented resistance to a minimum of 4 adequate depression treatments from at least 3 different categories; * In adult lifetime (\>21 year of age) have experience a period of wellness as defined by DSM IV criteria; * MADRS score ≥22 at 2 separate baseline visits, rated by 2 separate psychiatrists; * Global Assessment of Functioning (GAF) score \<50; * Mini-mental state examination (MMSE) score \>24; * No change in current antidepressant medication regimen or medication free for at least 4 weeks prior to study entry; * Able to give informed consent in accordance with institutional policies;

Exclusion criteria

* A diagnosis of bipolar I or bipolar II disorder by DSM-IV-TR criteria, derived from the MINI; * Meets criteria for borderline or antisocial personality disorder in the last 12 months by DSM-IV-TR criteria, derived from the Cluster B Personality Disorders Sections 301.7 - 301.83, preferably screened via Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II) at Baseline visit (optional); * In the current depressive episode, has been diagnosed with General Anxiety Disorder (GAD) - as defined by the DSM-IV-TR, and GAD is the primary diagnosis;

Design outcomes

Primary

Measure	Time frame	Description
Mean Percent Change From Baseline in MADRS Score	4, 7, 10 and 13 months	The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item scale that measures depressive symptom severity. Scores range from 9 to 60, with a higher score indicating more severe depression.

Secondary

Measure	Time frame	Description
Responder Rate (40% Reduction in MADRS)	4, 7, 10 and 13 months	—
Mean Percent Change From Baseline in Hamilton Anxiety Rating Scale (HAMA-A) Score	4, 7, 10 and 13 months	Developed by M. Hamilton, this widely-used interview scale measures the severity of a patient's anxiety, based on 14 parameters, including anxious mood, tension, fears, insomnia, somatic complaints and behavior at the interview. Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Mean Percent Change From Baseline in GAF Score	4, 7, 10 and 13 months	The Global Assessment Scale (GAF) is a hypothetical continuum of mental health illness that looks at psychological, social, and occupational functioning. It measures how much a person's symptoms affect their day-to-day life on a scale of 0 to 100. A score of 100-91 indicates no symptoms, 90-81 indicates absent minimal symptoms, 80-71 indicates symptoms that are transient and reactions expectable to psychosocial stressors, 70-61 indicates mild symptoms, 60-51 indicates moderate symptoms, 50-41 indicates serious symptoms, 40-31 indicates some impairment in reality testing or communication OR major impairment in several areas, 30-21 indicates delusions or hallucinations, 20-11 indicates danger of hurting self or others OR occasionally fails to maintain personal hygiene, 10-1 indicates persistent danger of severely hurting self or others OR persistent inability to maintain minimal personal hygiene OR serious suicidal act with clear expectation of death and 0 indicates inadequate data.
Mean Percent Change From Baseline in Quick Inventory of Depressive Symptoms - Self Report (QIDS-SR) Score	4, 7, 10 and 13 months	The Quick Inventory of Depressive Symptomatology Self Report (QIDS- SR) is a 16-question shortened self-test, derived from the 30-item Inventory of Depressive Symptomatology (IDS). Questions in the QIDS - SR-116 correlate with the nine Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). The severity of depression can be judged based on the total score. A score of 1-5 indicates No depression, 6-10 indicates Mild depression, 11-15 indicates Moderate depression, 16-20 indicates Severe depression and 21-27 indicates Very severe depression.
Mean Percent Change From Baseline in Hamilton Rating Scale for Depression (HDRS) Score	4, 7, 10 and 13 month	The Hamilton Depression Rating Scale is a 17-item scale that measures depressive symptom severity. Scores range from 0 to 52, with a higher score indicating more severe depression.
Mean Total CGI for Global Improvement Score	4, 7, 10 and 13 months	The CGI global improvement score ranges from 0-7 where 0 indicates not assessed; 1 indicates very much improved; 2 indicates much improved; 3 indicates minimally improved; 4 indicates no change; 5 indicates minimally worse; 6 indicates much worse; and 7 indicates very much worse.
Mean Percent Change From Baseline in Patient Global Impression Index (PGI) Severity of Illness	4, 7, 10 and 13 months	The CGI severity of illness scale is a simple validated, single-item, 7-point self-reported categorical scale ranging from 0-7 where 0 indicates not assessed; 1 indicates normal, not at all ill; 2 indicates borderline mentally ill; 3 indicates mildly ill; 4 indicates moderately ill; 5 indicates markedly ill; 6 indicates severely ill; and 7 indicates among the most severely ill patients.
Mean Total PGI for Global Improvement Score	4, 7, 10 and 13 months	The CGI global improvement score ranges from 0-7 where 0 indicates not assessed; 1 indicates very much improved; 2 indicates much improved; 3 indicates minimally improved; 4 indicates no change; 5 indicates minimally worse; 6 indicates much worse; and 7 indicates very much worse.
Mean Percent Change From Baseline in Clinical Global Impression of Severity and Improvement (CGI) Severity of Illness	4, 7, 10 and 13 months	The CGI severity of illness scale is a simple validated, single-item, 7-point self-reported categorical scale ranging from 0-7 where 0 indicates not assessed; 1 indicates normal, not at all ill; 2 indicates borderline mentally ill; 3 indicates mildly ill; 4 indicates moderately ill; 5 indicates markedly ill; 6 indicates severely ill; and 7 indicates among the most severely ill patients.

Countries

France, Israel, United Kingdom

Participant flow

Participants by arm

Arm	Count
Group 1 : High Frequency Group Group 1 : DBS High Frequency (HF) Group Device Programming (130 Hz) Implanted with investigational device and activated for stimulation.	5
Group 2 : Low Frequency Group Group 2 : DBS Low Frequency (LF) Group Device Programming (20 Hz) Implanted with investigational device and activated for stimulation.	4
Total	9

Baseline characteristics

Characteristic	Group 1 : High Frequency Group	Group 2 : Low Frequency Group	Total
Age, Continuous	43 years	51 years	46 years
Region of Enrollment France	1 participants	0 participants	1 participants
Region of Enrollment Israel	2 participants	2 participants	4 participants
Region of Enrollment United Kingdom	2 participants	2 participants	4 participants
Sex: Female, Male Female	2 Participants	3 Participants	5 Participants
Sex: Female, Male Male	3 Participants	1 Participants	4 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 5	0 / 4
other Total, other adverse events	4 / 5	4 / 4
serious Total, serious adverse events	1 / 5	0 / 4

Outcome results

Primary

Mean Percent Change From Baseline in MADRS Score

The Montgomery-Asberg Depression Rating Scale (MADRS) is a 10-item scale that measures depressive symptom severity. Scores range from 9 to 60, with a higher score indicating more severe depression.

Time frame: 4, 7, 10 and 13 months