DepressionEarly Phase 1NCT00555698
Feasibility, Safety and Efficacy of Deep Brain Stimulation for Depression
A Early Phase 1 study testing Deep Brain Stimulations for Depression in people with Depression, run by Ali Rezai, MD at 1 site in United States.
Trial summary
The purpose of this investigation is to obtain a preliminary indication of the feasibility, safety and efficacy of capsular deep brain stimulation (DBS) as a treatment for intractable depression. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Depression
- What is being tested?
- Deep Brain Stimulations for Depression
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Feb 2011
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Major depression, severe, unipolar type, diagnosed by Structured Clinical Interview for DSM-IV (SCID-IV), judged to be of disabling severity
- 24-item Hamilton Depression Rating Scale (HDRS) score of at least 21
- Global Assessment of Function (GAF) score of 45 or less.
- A recurrent (>4 episodes) or chronic (episode duration >2 years) course and a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior).
- Failure to respond to:
- adequate trials (>6 weeks at the maximum recommended or tolerated dose) of primary antidepressants from at least 3 different classes and;
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- adequate trials (>4 weeks at the usually recommended or maximum tolerated dose) of augmentation/combination of a primary antidepressant using at least 2 different augmenting/combination agents (lithium, T3, stimulants, neuroleptics, anticonvulsants, buspirone, or a second primary antidepressant) and;
- an adequate trial of ECT (>6 bilateral treatments) and;
- an adequate trial of individual psychotherapy (>20 sessions with an experienced psychotherapist).
- Age 18 - 55 years.
- Able to comply with the operational and administrative requirements of participation in the study.
- Able to give written informed consent.
- Either drug-free or on a stable drug regimen for at least 6 weeks at the time of entry into the study.
- Good general health.
Who cannot join
- Current or past nonaffective psychotic disorder.
- Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome.
- Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI)
- Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/or inability to undergo presurgical MRI (cardiac pacemaker, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac or other medical risk factors for surgery.
- Current or unstably remitted substance abuse.
- Pregnancy and women of childbearing age not using effective contraception.
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- History of severe personality disorder.
- Imminent risk of suicide (based on the judgment of the investigators).
- Not able to comply with the operational and administrative requirements of participation in the study (based on the judgment of the investigators).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Feasibility, Safety and Efficacy of Deep Brain Stimulation of the Internal Capsule for Severe and Medically Refractory Major Depression
The purpose of this investigation is to obtain a preliminary indication of the feasibility, safety and efficacy of capsular deep brain stimulation (DBS) as a treatment for intractable depression. Also, to to learn about a new treatment for severe depression that has not improved enough despite long-term treatment with medications and behavior therapy. The new treatment is called deep brain stimulation, or DBS.
In DBS, thin wires are used to carry electric current to parts of the brain that are thought to be involved in producing depression symptoms. Two wires are implanted surgically, and attached to battery packs implanted under the skin of the new chest below your collar bone.
Read the detailed description
This protocol proposes a pilot/feasibility clinical study of therapeutic benefits of ventral capsule/ventral striatum deep brain stimulation (DBS) as a treatment in ten patients with intractable major depression (MD). Conservative estimates place MD's prevalence at 2.6% to 5.5% in men and 6.0% to 11.8% in women. Most conservative studies estimate a 20% complete refractoriness to medical and psychotherapeutic regimens. Given the prevalence of major depression in the general population, over 3.5 million Americans would be expected to manifest refractory illness if all those with depression received treatment. Study subjects will have MD of disabling severity, intractable to prolonged treatment attempts with conventional medication and pschotherapies. They must also have had electroconvulsive therapy. These refractory patients would be candidates for a destructive/lesioning brain surgery such as a radiofrequency cingulotomy.
These MD patients are analogous to medically intractable Parkinson's disease and tremor patients who until recently underwent similar destructive surgeries such as a pallidotomy or thalamotomy. The use of DBS technology with its inherent advantage of being fully reversible and adjustable has become standard of care for these disabled patients. Studies have demonstrated improved safety and efficacy of DBS over lesioning.
Recently, DBS technology has been employed in the lesioning target of the anterior limb of the internal capsule for OCD. These preliminary studies in Europe and now the US, are demonstrating improved outcomes for refractory OCD patients with regard to their OC symptoms as well as depressed mood. This amelioration of mood provides the basis on which anterior internal capsule DBS may help major depression patients.
Based on this rationale, we believe that DBS is a viable therapeutic surgical option in this group of severely ill MD patients. The standard DBS stereotactic surgical techniques employed by the CCF team in hundreds of movement disorder patients will be used. The DBS electrodes will be implanted bilaterally in the anterior limb of the internal capsule and connected subcutaneously to subclavicular programmable pulse generators.
- Conditions
- Depression
- Being tested
- Deep Brain Stimulations for Depression
- Keywords
- DBS, Depression
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep Brain Stimulations for DepressionDevice
Deep Brain Stimulations for Depression
| Study group | Role | What they receive |
|---|---|---|
| DBS | Experimental | DBS Receives: Device: Deep Brain Stimulations for Depression |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS)
Measured: These scales are administered on each postoperative clinic visit. Visits occur monthly, except during the open continuation phase, when they occur every three months.
Secondary outcomes (1)
Inventory for Depressive Symptoms, Self-report (IDS-SR), Clinical Global Impressions (CGI), Patient Global Impressions (PGI), Global Assessment of Functioning (GAF), Social and Occupational Function Assessment Scale (SOFAS), Quality of LIfe Enjoyment and
Measured: These measures will be obtained at baseline, at the end of the initial chronic phase (typically after three months of chronic stimultion), at the end of the open continuation phase (at two years into the study).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2007 (estimated)
- Study startJan 2004
- Primary completionFeb 2011
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ali Rezai, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Medtronic, The Cleveland Clinic
- Responsible party
- Sponsor-investigator, Ali Rezai, MD, Ohio State University
- Investigators
- Ali Rezai, MD, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00555698
- Sponsor's protocol ID
- 6577
- Status last verified
- Mar 2017
- First submitted
- 7 Nov 2007
- Last updated
- 28 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF, Salloway SP, Okun MS, Goodman WK, Rasmussen SA. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006 Nov;31(11):2384-93. doi: 10.1038/sj.npp.1301165. Epub 2006 Jul 19.
PubMed 16855529
Study at a glance
From the registry record, last updated by the sponsor on 28 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Feasibility, Safety and Efficacy of Deep Brain Stimulation of the Internal Capsule for Severe and Medically Refractory Major Depression
- ClinicalTrials.gov ID
- NCT00555698
- Acronym / sponsor ID
- 6577
- Conditions
- Depression
- Keywords
- DBS, Depression
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Ali Rezai, MDUniversity, hospital or other
- Collaborators
- Medtronic, The Cleveland Clinic
- Study start
- Jan 2004
- Primary completion
- Feb 2011 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 9 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this investigation is to obtain a preliminary indication of the feasibility, safety and efficacy of capsular deep brain stimulation (DBS) as a treatment for intractable depression. Also, to to learn about a new treatment for severe depression that has not improved enough despite long-term treatment with medications and behavior therapy. The new treatment is called deep brain stimulation, or DBS.
In DBS, thin wires are used to carry electric current to parts of the brain that are thought to be involved in producing depression symptoms. Two wires are implanted surgically, and attached to battery packs implanted under the skin of the new chest below your collar bone.
Detailed description
This protocol proposes a pilot/feasibility clinical study of therapeutic benefits of ventral capsule/ventral striatum deep brain stimulation (DBS) as a treatment in ten patients with intractable major depression (MD). Conservative estimates place MD's prevalence at 2.6% to 5.5% in men and 6.0% to 11.8% in women. Most conservative studies estimate a 20% complete refractoriness to medical and psychotherapeutic regimens. Given the prevalence of major depression in the general population, over 3.5 million Americans would be expected to manifest refractory illness if all those with depression received treatment. Study subjects will have MD of disabling severity, intractable to prolonged treatment attempts with conventional medication and pschotherapies. They must also have had electroconvulsive therapy. These refractory patients would be candidates for a destructive/lesioning brain surgery such as a radiofrequency cingulotomy.
These MD patients are analogous to medically intractable Parkinson's disease and tremor patients who until recently underwent similar destructive surgeries such as a pallidotomy or thalamotomy. The use of DBS technology with its inherent advantage of being fully reversible and adjustable has become standard of care for these disabled patients. Studies have demonstrated improved safety and efficacy of DBS over lesioning.
Recently, DBS technology has been employed in the lesioning target of the anterior limb of the internal capsule for OCD. These preliminary studies in Europe and now the US, are demonstrating improved outcomes for refractory OCD patients with regard to their OC symptoms as well as depressed mood. This amelioration of mood provides the basis on which anterior internal capsule DBS may help major depression patients.
Based on this rationale, we believe that DBS is a viable therapeutic surgical option in this group of severely ill MD patients. The standard DBS stereotactic surgical techniques employed by the CCF team in hundreds of movement disorder patients will be used. The DBS electrodes will be implanted bilaterally in the anterior limb of the internal capsule and connected subcutaneously to subclavicular programmable pulse generators.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| DBS | Experimental | Device: Deep Brain Stimulations for DepressionDBS |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- Major depression, severe, unipolar type, diagnosed by Structured Clinical Interview for DSM-IV (SCID-IV), judged to be of disabling severity
- 24-item Hamilton Depression Rating Scale (HDRS) score of at least 21
- Global Assessment of Function (GAF) score of 45 or less.
- A recurrent (>4 episodes) or chronic (episode duration >2 years) course and a minimum of 5 years since the onset of the first depressive episode. Major impairment in functioning or potentially severe medical outcomes (repeated hospitalizations, serious suicidal or other self-injurious behavior).
- Failure to respond to:
Key exclusion criteria (9 listed)
- Current or past nonaffective psychotic disorder.
- Any current clinically significant neurological disorder or medical illness affecting brain function, other than motor tics or Gilles de la Tourette syndrome.
- Any clinically significant abnormality on preoperative magnetic resonance imaging (MRI)
- Any surgical contraindications to undergoing DBS, including labeled contraindications for DBS and/or inability to undergo presurgical MRI (cardiac pacemaker, pregnancy, metal in body, severe claustrophobia), infection, coagulopathy, inability to undergo an awake operation, significant cardiac or other medical risk factors for surgery.
- Current or unstably remitted substance abuse.
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 |
|---|---|---|
| Deep Brain Stimulations for DepressionDeep Brain Stimulations for Depression | Device | DBS |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS)
Time frame: These scales are administered on each postoperative clinic visit. Visits occur monthly, except during the open continuation phase, when they occur every three months.
1 secondary outcome
Inventory for Depressive Symptoms, Self-report (IDS-SR), Clinical Global Impressions (CGI), Patient Global Impressions (PGI), Global Assessment of Functioning (GAF), Social and Occupational Function Assessment Scale (SOFAS), Quality of LIfe Enjoyment and
Time frame: These measures will be obtained at baseline, at the end of the initial chronic phase (typically after three months of chronic stimultion), at the end of the open continuation phase (at two years into the study).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Mar 2017.
- Background: PubMed 16855529Greenberg BD, Malone DA, Friehs GM, Rezai AR, Kubu CS, Malloy PF, Salloway SP, Okun MS, Goodman WK, Rasmussen SA. Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder. Neuropsychopharmacology. 2006 Nov;31(11):2384-93. doi: 10.1038/sj.npp.1301165. Epub 2006 Jul 19.
- Individual participant dataSharing planned: No
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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.
Ali Rezai, MD principal investigator
The Cleveland Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Deep Brain Stimulations for Depression in people with Depression, run by Ali Rezai, MD 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?
The sponsor lists 14 inclusion and 9 exclusion criteria. 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 28 Mar 2017. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Montgomery-Asberg Depression Rating Scale (MADRS), Hamilton Depression Rating Scale (HDRS) (time frame: These scales are administered on each postoperative clinic visit. Visits occur monthly, except during the open continuation phase, when they occur every three months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00555698, which also lists 1 linked publication.
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 28 Mar 2017; AzTrials last refreshed its copy on 7 Nov 2026.