Treatment Resistant DepressionNCT01898429
Deep Brain Stimulation (DBS) for Treatment-Resistant Depression (TRD)
A study testing SCC DBS in people with Treatment Resistant Depression and Depressive Disorder, Treatment-Resistant, run by Paul Holtzheimer at 1 site in United States.
Trial summary
In this pilot study, we propose to test whether high frequency stimulation of the subcallosal cingulate (SCC) is a safe and efficacious antidepressant treatment in five TRD patients, to compare the effects of left-sided vs. Read more about this study
- Who is it for?
- Ages 22 to 70 years
- Conditions the study is for
- Treatment Resistant Depression, Depressive Disorder, Treatment-Resistant, Depression, Bipolar
- What is being tested?
- SCC DBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Dec 2016
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
A partial list of eligibility criteria includes:
- Age 18-70 years old
- Ability to provide written informed consent
- Current Major Depressive Episode (MDE), secondary to either Major Depressive Disorder or Bipolar Disorder (I, II or NOS)
- A current depressive episode of at least 12 months duration
- For patients with a bipolar disorder, the last hypomanic or manic episode must have been at least 2 years before study entry
- A maximum Global Assessment of Functioning of 50
- Able to tolerate general anesthesia, DBS surgery and MRI scans
- No significant cerebrovascular risk factors or a previous stroke, documented major head trauma or neurodegenerative disorder
- No currently active clinically significant Axis I psychiatric diagnosis or a personality disorder likely to interfere with the study
- No evidence of global cognitive impairment
- Lives locally or willing to relocate to the area for up to One Year
Trial locations and contacts
1 site in 1 country.
United States1 site
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, 03756
About this study
Official title: Deep Brain Stimulation for Treatment-Resistant Depression
In this pilot study, we propose to test whether high frequency stimulation of the subcallosal cingulate (SCC) is a safe and efficacious antidepressant treatment in five TRD patients, to compare the effects of left-sided vs. right-sided stimulation, and to investigate potential mechanisms of action of this intervention. Importantly, this study will be used to assess the need for and assist in planning a larger, more definitive trial of SCC DBS for TRD.
Read the detailed description
The U.S. lifetime prevalence of major depressive disorder (MDD) is 17%. A number of treatments are available for depression including medications, psychotherapy and various somatic treatments. Unfortunately, up to two-thirds of patients remain symptomatic following first-line treatment and a third fail to achieve remission (defined as full resolution of depressive symptoms) after four established treatments; approximately 10%-20% of depressed patients may show virtually no improvement despite multiple, often aggressive treatments. Thus, a conservative estimate places the U.S. prevalence of treatment-resistant depression (TRD) at 1%-3%. TRD has a high risk of suicide, is a major cause of disability and is responsible for doubling of overall health care costs.
For patients with TRD there are limited evidence-based treatment options. Transcranial magnetic stimulation (TMS) may have efficacy for patients that have failed no more than one antidepressant medication 10-12, but response and remission rates are relatively low (under 30% and 20% respectively). Vagus nerve stimulation (VNS) may have efficacy in patients that have failed 4-6 antidepressant treatments but long-term response and remission rates are again low (about 20% and 10% respectively). Electroconvulsive therapy(ECT) can be effective in TRD patients with remission rates of 50%-60%. However, more than 70% of TRD patients will relapse within 6 months following a successful acute treatment course. For patients that have failed ECT, there are no evidence-based treatment options. Therefore, there is great need for novel treatment approaches for TRD.
Prior clinical trials have shown that SCC DBS has the potential to be a valuable treatment option for patients with TRD. Further developing this treatment will involve confirming its effectiveness and identifying ways to optimize its use. In this study we intend to test the safety and efficacy of chronic SCC DBS as a treatment for TRD and compare the safety and efficacy of left-sided versus right-sided stimulation using a double-blind, randomized, cross-over design.
- Conditions
- Treatment Resistant Depression, Depressive Disorder, Treatment-Resistant, Depression, Bipolar
- Being tested
- SCC DBS
- Keywords
- Treatment Resistant Depression, Treatment Refractory Depression, Treatment Resistant Bipolar Disorder, Treatment Refractory Bipolar Disorder, Deep brain stimulation, DBS
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SCC DBSDevice
Also called Libra(TM) Implantable Deep Brain Stimulation (DBS) System
Deep Brain Stimulator
| Study group | Role | What they receive |
|---|---|---|
| Left-sided SCC DBS | Active comparator | Active Stimulation of the left-sided electrode Receives: Device: SCC DBS |
| Right-sided SCC DBS | Active comparator | Active stimulation of the right-sided electrode Receives: Device: SCC DBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of 12 Weeks of Left Unilateral DBS vs. 12 Weeks Right Unilateral DBS on Change in 17-item Hamilton Depression Rating Scale (HDRS-17)
Baseline HDRS-17 is defined as the average of 4 weekly HDRS-17 in the 4 weeks leading up to surgery. Change in HDRS-17 after 12 weeks of left-sided stimulation (compared to baseline) will be compared to change in HDRS-17 after 12 weeks of right-sided stimulation (compared to baseline). The scale ranges from 0-48 with higher scored indicating more severe depression. A cutoff of 7 or below is considered remission from depression. A decrease of at least 50% from baseline is considered an antidepressant response.
Measured: baseline, 12 weeks of phase 1, 12 weeks of phase 2 and 12 weeks of phase 3 (bilateral stimulation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2013 (estimated)
- Study startJul 2013
- Primary completionDec 2016
- Study completionDec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Paul Holtzheimer
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Paul Holtzheimer, Dartmouth-Hitchcock Medical Center
- Investigators
- Paul E Holtzheimer, MD, Principal investigator, Dartmouth-Hitchcock Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01898429
- Sponsor's protocol ID
- D12051
- Other IDs
- 23293
- Status last verified
- Jul 2019
- First submitted
- 9 Jul 2013
- Last updated
- 25 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation for Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT01898429
- Acronym / sponsor ID
- D12051
- Conditions
- Treatment Resistant Depression, Depressive Disorder, Treatment-Resistant, Depression, Bipolar
- Keywords
- Treatment Resistant Depression, Treatment Refractory Depression, Treatment Resistant Bipolar Disorder, Treatment Refractory Bipolar Disorder, Deep brain stimulation, DBS
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Paul HoltzheimerUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 12 Jul 2013 (estimated)
- Results
- Posted 12 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this pilot study, we propose to test whether high frequency stimulation of the subcallosal cingulate (SCC) is a safe and efficacious antidepressant treatment in five TRD patients, to compare the effects of left-sided vs. right-sided stimulation, and to investigate potential mechanisms of action of this intervention. Importantly, this study will be used to assess the need for and assist in planning a larger, more definitive trial of SCC DBS for TRD.
Detailed description
The U.S. lifetime prevalence of major depressive disorder (MDD) is 17%. A number of treatments are available for depression including medications, psychotherapy and various somatic treatments. Unfortunately, up to two-thirds of patients remain symptomatic following first-line treatment and a third fail to achieve remission (defined as full resolution of depressive symptoms) after four established treatments; approximately 10%-20% of depressed patients may show virtually no improvement despite multiple, often aggressive treatments. Thus, a conservative estimate places the U.S. prevalence of treatment-resistant depression (TRD) at 1%-3%. TRD has a high risk of suicide, is a major cause of disability and is responsible for doubling of overall health care costs.
For patients with TRD there are limited evidence-based treatment options. Transcranial magnetic stimulation (TMS) may have efficacy for patients that have failed no more than one antidepressant medication 10-12, but response and remission rates are relatively low (under 30% and 20% respectively). Vagus nerve stimulation (VNS) may have efficacy in patients that have failed 4-6 antidepressant treatments but long-term response and remission rates are again low (about 20% and 10% respectively). Electroconvulsive therapy(ECT) can be effective in TRD patients with remission rates of 50%-60%. However, more than 70% of TRD patients will relapse within 6 months following a successful acute treatment course. For patients that have failed ECT, there are no evidence-based treatment options. Therefore, there is great need for novel treatment approaches for TRD.
Prior clinical trials have shown that SCC DBS has the potential to be a valuable treatment option for patients with TRD. Further developing this treatment will involve confirming its effectiveness and identifying ways to optimize its use. In this study we intend to test the safety and efficacy of chronic SCC DBS as a treatment for TRD and compare the safety and efficacy of left-sided versus right-sided stimulation using a double-blind, randomized, cross-over design.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Left-sided SCC DBS | Active comparator | Device: SCC DBSActive Stimulation of the left-sided electrode |
| Right-sided SCC DBS | Active comparator | Device: SCC DBSActive stimulation of the right-sided electrode |
Who may qualify
- Ages
- 22 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SCC DBSAlso: Libra(TM) Implantable Deep Brain Stimulation (DBS) SystemDeep Brain Stimulator | Device | Left-sided SCC DBS, Right-sided SCC DBS |
Primary outcome
Comparison of 12 Weeks of Left Unilateral DBS vs. 12 Weeks Right Unilateral DBS on Change in 17-item Hamilton Depression Rating Scale (HDRS-17)
Time frame: baseline, 12 weeks of phase 1, 12 weeks of phase 2 and 12 weeks of phase 3 (bilateral stimulation)
Baseline HDRS-17 is defined as the average of 4 weekly HDRS-17 in the 4 weeks leading up to surgery. Change in HDRS-17 after 12 weeks of left-sided stimulation (compared to baseline) will be compared to change in HDRS-17 after 12 weeks of right-sided stimulation (compared to baseline). The scale ranges from 0-48 with higher scored indicating more severe depression. A cutoff of 7 or below is considered remission from depression. A decrease of at least 50% from baseline is considered an antidepressant response.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul E Holtzheimer, MD principal investigator
Dartmouth-Hitchcock Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing SCC DBS in people with Treatment Resistant Depression and Depressive Disorder, Treatment-Resistant, run by Paul Holtzheimer at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of 12 Weeks of Left Unilateral DBS vs. 12 Weeks Right Unilateral DBS on Change in 17-item Hamilton Depression Rating Scale (HDRS-17) (time frame: baseline, 12 weeks of phase 1, 12 weeks of phase 2 and 12 weeks of phase 3 (bilateral stimulation)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2019.