Depression
Conditions
Keywords
Treatment Resistant Depression, Treatment Refractory Depression, Deep Brain Stimulation, Depression
Brief summary
Medtronic, Inc. sponsored an investigational study of the Reclaim™ Deep Brain Stimulation (DBS) System in people that have treatment-resistant depression. Depression is a mood disorder and a serious medical condition that affects millions of Americans. Depressive symptoms may include loss of interest in things typically enjoyed; decreased energy levels; difficulty concentrating or making decisions; restlessness; and feelings of pessimism, hopelessness, and worthlessness. Treatment-resistant depression is a chronic and severe form of depression characterized by failure to respond to traditional forms of treatment, such as antidepressant medications and electroconvulsive therapy. Treatment-resistant depression significantly impacts quality of life, productivity, and is a major contributor of disability world-wide. This randomized, double-blind, sham stimulation-controlled, multi-center, prospective, parallel design study used deep brain stimulation technology to test whether active bilateral stimulation can safely and effectively improve depressive symptoms in patients with treatment-resistant depression compared to sham stimulation. Participants meeting criteria for the study were implanted with the Reclaim DBS System. Participants in the active group, who received active stimulation, were compared to the control group, who received sham stimulation, during the 16-week blinded-treatment phase. All participants were monitored for changes in depressive symptoms. After the blinded-treatment phase, all participants received active stimulation. Candidates for the trial were adults who had major depressive disorder and had not responded to several treatments for depression. Participants in the study continued to receive their current antidepressant medications while participating in the trial.
Interventions
DEVICEReclaim™ DBS System
Sponsors
MedtronicNeuro
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Consent to participate in screening and study procedures by signing and dating the Informed Consent Form * Are diagnosed with major depressive disorder (MDD) * Have tried at least 4 different treatments, for example antidepressant medications, combinations of antidepressant medications, and/or electroconvulsive therapy (ECT) * Screening MADRS score ≥ 28 * Have had the current major depressive episode persist for at least 2 years * Females, if of child-bearing potential, must be using an acceptable method of birth control
Exclusion criteria
* Females: Currently pregnant * Currently enrolled in or plan to enroll in any concurrent drug and/or device study that may confound the results of this study * Have a neurological condition that may jeopardize the safety or the conduct of the study * Have any medical conditions unsuitable for undergoing DBS surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Responders | Baseline to 16 weeks | Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression Change | Baseline to 16 weeks | Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Improvement is measured by the groups' mean percent change in MADRS score. An improvement is represented by a decline in MADRS (a negative percent change). |
| Quality of Life Change | Baseline to 16 weeks | Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF); total score can range from 0 to 100 with higher scores indicating a better quality of life. Improvement is measured by the groups' mean change in Q-LES-Q-SF score. An improvement is represented by an increase in Q-LES-Q-SF (a positive change). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Long-term Open-label Responders | at the 24-month visit | This measure is for long-term, open-label stimulation. Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response. All enrolled participants are included in the analysis, even if they withdrew early. Participants that withdrew early are counted as non-responders. |
| Therapy-related Adverse Events | from enrollment to study closure (average follow-up of 36 months) | Adverse events related to the device, implant procedure, and/or stimulation are reported. Events with a prevalence of greater than 5% of subjects are reported. This measure describes the experience of all study participants (both Active and Control Groups combined), and includes the operative, blinded-treatment,and the long-term open-label follow-up phases combined. Active Group participants began therapy after randomization, while Control Group participants began therapy after 16 weeks of sham stimulation. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active Group-Active Stimulation Receive active stimulation during the first 16 weeks after device implant. | 16 |
| Control Group-Sham Stimulation Receive sham stimulation during the first 16 weeks after device implant. | 14 |
| Total | 30 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Blinded-treatment Phase | Physician Decision | 1 | 0 |
| Long-term Follow-up Phase - Open Label | Death | 1 | 0 |
| Long-term Follow-up Phase - Open Label | Physician Decision | 2 | 0 |
| Long-term Follow-up Phase - Open Label | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Active Group-Active Stimulation | Control Group-Sham Stimulation | Total |
|---|---|---|---|
| Age, Continuous | 46.6 years STANDARD_DEVIATION 14.4 | 48.9 years STANDARD_DEVIATION 8.9 | 47.7 years STANDARD_DEVIATION 12 |
| Baseline depression score | 37.0 units on a scale STANDARD_DEVIATION 5.1 | 36.4 units on a scale STANDARD_DEVIATION 3.3 | 36.7 units on a scale STANDARD_DEVIATION 4.3 |
| Region of Enrollment United States | 16 participants | 14 participants | 30 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 8 Participants | 9 Participants | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 16 | 14 / 14 |
| serious Total, serious adverse events | 4 / 16 | 4 / 14 |
Outcome results
Primary
Responders
Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response.
Time frame: Baseline to 16 weeks
Population: 29 of the 30 subjects are included in this analysis. One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Group-Active Stimulation | Responders | 3 participants |
| Control Group-Sham Stimulation | Responders | 2 participants |
Comparison: The study originally required a sample size of 208 subjects in order to have 90% power to detect a statistically significant difference between the responder rate of the active and control groups. With this 30-subject cohort, and only 29 subjects completing the blinded-treatment phase per protocol, the comparison of response rates was not adequately powered. The P-value is presented only to describe the outcomes of the two groups.p-value: =0.53Fisher Exact
Secondary
Depression Change
Montgomery-Åsberg Depression Rating Scale (MADRS); total score can range from 0 (no symptoms) to 60 (severe depression). Improvement is measured by the groups' mean percent change in MADRS score. An improvement is represented by a decline in MADRS (a negative percent change).
Time frame: Baseline to 16 weeks
Population: One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Group-Active Stimulation | Depression Change | -19.6 percentage change from baseline | Standard Deviation 34.9 |
| Control Group-Sham Stimulation | Depression Change | -24.6 percentage change from baseline | Standard Deviation 28.8 |
Secondary
Quality of Life Change
Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF); total score can range from 0 to 100 with higher scores indicating a better quality of life. Improvement is measured by the groups' mean change in Q-LES-Q-SF score. An improvement is represented by an increase in Q-LES-Q-SF (a positive change).
Time frame: Baseline to 16 weeks
Population: One active group subject did not receive the allocated treatment, and is not included in the primary and secondary efficacy outcome analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active Group-Active Stimulation | Quality of Life Change | 10.2 change from baseline score | Standard Deviation 24.8 |
| Control Group-Sham Stimulation | Quality of Life Change | 9.8 change from baseline score | Standard Deviation 18.8 |
Other Pre-specified
Long-term Open-label Responders
This measure is for long-term, open-label stimulation. Response is defined as at least a 50% improvement (decline) in MADRS score. Responder rate is the proportion of participants who experience response. All enrolled participants are included in the analysis, even if they withdrew early. Participants that withdrew early are counted as non-responders.
Time frame: at the 24-month visit
Population: 29 participants started the the Long-Term Follow-up Phase and 24 completed the phase, but all 30 enrolled participants are included in the analysis. Participants that withdrew early are counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active Group-Active Stimulation | Long-term Open-label Responders | 7 participants |
Other Pre-specified
Therapy-related Adverse Events
Adverse events related to the device, implant procedure, and/or stimulation are reported. Events with a prevalence of greater than 5% of subjects are reported. This measure describes the experience of all study participants (both Active and Control Groups combined), and includes the operative, blinded-treatment,and the long-term open-label follow-up phases combined. Active Group participants began therapy after randomization, while Control Group participants began therapy after 16 weeks of sham stimulation.
Time frame: from enrollment to study closure (average follow-up of 36 months)
Population: All enrolled participants are included in the analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Disturbance in attention | 4 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Sleep disorder | 5 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Device - Implant site pain | 7 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Device - Paraesthesia | 4 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Procedure - Implant site pain | 8 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Procedure - Implant site infection | 5 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Procedure - Dermatitis contact | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Procedure - Face oedema | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Procedure - Headache | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Procedure - Hypersensitivity | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Insomnia | 15 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Depression | 8 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Hypomania | 8 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Irritability | 8 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Anxiety | 7 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Fatigue | 6 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Headache | 6 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Agitation | 5 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Suicidal ideation | 4 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Disinhibition | 3 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Memory impairment | 3 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Paraesthesia | 3 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Energy increased | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Impulsive behaviour | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Nausea | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Thinking abnormal | 2 participants |
| Active Group-Active Stimulation | Therapy-related Adverse Events | Stimulation - Weight increased | 2 participants |