DepressionPhase 2/3NCT00149838
Magnetic Brain Stimulation for the Treatment of Adult Depression
A Phase 2/3 study testing Prefrontal rTMS and Antidepressant Regimen in people with Depression, run by Medical University of South Carolina at 4 sites in United States.
Trial summary
This study will evaluate the safety and effectiveness of magnetic brain stimulation for the treatment of major depression in depressed adults with moderate treatment resistance. Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Depression
- What is being tested?
- Prefrontal rTMS and Antidepressant Regimen
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 190 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2005to May 2009
- Phase
- Phase 2/3
- 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 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of major depression with a current episode
- Hamilton Rating Scale for Depression score higher than 20
- No response or intolerance to antidepressant medication in the current depressive episode
Who cannot join
- Current use of antidepressants
- Diagnosis of psychosis or anxiety disorder
- Current substance abuse
- Seizures or history of head trauma
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Emory University
Atlanta, Georgia, 30329-5102
Brain Stimulation Laboratory, Medical University of South Carolina
Charleston, South Carolina, 29425
Columbia University
New York, New York, 10032
University of Washington
Seattle, Washington, 98104-2499
About this study
Official title: Optimization of Transcranial Magnetic Stimulation (TMS) for Depression
This study will evaluate the safety and effectiveness of magnetic brain stimulation for the treatment of major depression in depressed adults with moderate treatment resistance.
Read the detailed description
Major depression is a type of depression that can interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Because people often develop resistances to medications used to treat depression, new treatments are needed. Decreased electrical activity in the prefrontal region of the brain has been linked to some symptoms of depression. Repetitive transcranial magnetic stimulation (rTMS) can be used to influence the brain's electrical activity. This procedure entails attaching electrodes to the head and using a device to pass magnetic energy through coils and into the brain. rTMS has been shown to have antidepressant effects in depressed individuals. However, optimal levels of intensity and treatment duration have yet to be determined. This study will assess the safety and effectiveness of rTMS on the prefrontal region of the brain in depressed adults with moderate treatment resistance.
The treatment phase of this double-blind study will last a minimum of 32 weeks and will consist of 3 phases. In Phase I, participants will be randomly assigned to receive either rTMS or sham stimulation. The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. In Phase II, participants who were unresponsive to Phase I treatment will receive daily rTMS at a lower dose for 3 weeks. Participants who show signs of improvement, but have not achieved remission, may continue Phase II for 4 additional weeks. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual differences in cortical to skull distances. Phase III participants will be only those who achieved remission in the first 2 phases. These participants will receive antidepressant medication treatment daily for six months. Participants' functional status and symptoms of depression will be measured using self-report scales and video-recorded interviews at study start date and at the end of each treatment phase.
- Conditions
- Depression
- Being tested
- Prefrontal rTMS, Antidepressant Regimen, Sham Stimulation
- Keywords
- Electric Stimulation, Magnetic Stimulation, Prefrontal Cortex, Brain
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prefrontal rTMSProcedure or surgery
Also called TMS, rTMS
Participants receive 120% motor threshold (MT) over left and right prefrontal cortex. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks.
Antidepressant RegimenDrug
Also called medication
Particpants who acheive remission with rTMS may start antidepressant medication in phase III.
Sham StimulationProcedure or surgery
The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Active prefrontal rTMS phase1 | Experimental | Phase I participants receiving rTMS Receives: Procedure: Prefrontal rTMS |
| Sham rTMS phase 1 | Placebo comparator | Phase I participants receiving sham stimulation Receives: Procedure: Sham Stimulation |
| rTMS extension | Experimental | rTMS. Phase II participants, all of whom did not meet remission requirements after phase 1. They all receive active open label rTMS Receives: Procedure: Prefrontal rTMS |
| Open label antidepressant regimen | Experimental | All patients who met remission who were then transitioned to medications after the TMS trial was completed. Receives: Drug: Antidepressant Regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depression Remission, as Measured by the Hamilton Rating Scale for Depression
The Hamilton Rating Scale for Depression 17-item total score ranges from 0 to 52 with higher scores indicating more depression. Remission is defined as a total score of ≤ 8
Measured: Measured at the end of Phases 1, 2, and 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2005 (estimated)
- Study startFeb 2005
- Primary completionApr 2009
- Study completionMay 2009
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 190 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of South Carolina
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Mark S. George, MD, Principal investigator, Medical University of South Carolina
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00149838
- Sponsor's protocol ID
- R01MH069887
- Other IDs
- R01MH069887, DATR A5-ETMA
- Status last verified
- Dec 2018
- First submitted
- 6 Sep 2005
- Last updated
- 28 Dec 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Interested researchers can email the PI, Dr. George, with a request and how they plan to analyze the data. He will then make available a de-identified copy of the data.
Publications
Borckardt JJ, Nahas ZH, Teal J, Lisanby SH, McDonald WM, Avery D, Durkalski V, Pavlicova M, Long JM, Sackeim HA, George MS. The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial. Brain Stimul. 2013 Nov;6(6):925-8. doi: 10.1016/j.brs.2013.04.009. Epub 2013 May 21.
PubMed 23769413George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
PubMed 20439832
Study at a glance
From the registry record, last updated by the sponsor on 28 Dec 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimization of Transcranial Magnetic Stimulation (TMS) for Depression
- ClinicalTrials.gov ID
- NCT00149838
- Acronym / sponsor ID
- R01MH069887
- Conditions
- Depression
- Keywords
- Electric Stimulation, Magnetic Stimulation, Prefrontal Cortex, Brain
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 190 participants (actual)
- Lead sponsor
- Medical University of South CarolinaUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- Feb 2005
- Primary completion
- Apr 2009 (actual)
- Study completion
- May 2009 (actual)
- First posted
- 8 Sep 2005 (estimated)
- Results
- Posted 28 Dec 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the safety and effectiveness of magnetic brain stimulation for the treatment of major depression in depressed adults with moderate treatment resistance.
Detailed description
Major depression is a type of depression that can interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Because people often develop resistances to medications used to treat depression, new treatments are needed. Decreased electrical activity in the prefrontal region of the brain has been linked to some symptoms of depression. Repetitive transcranial magnetic stimulation (rTMS) can be used to influence the brain's electrical activity. This procedure entails attaching electrodes to the head and using a device to pass magnetic energy through coils and into the brain. rTMS has been shown to have antidepressant effects in depressed individuals. However, optimal levels of intensity and treatment duration have yet to be determined. This study will assess the safety and effectiveness of rTMS on the prefrontal region of the brain in depressed adults with moderate treatment resistance.
The treatment phase of this double-blind study will last a minimum of 32 weeks and will consist of 3 phases. In Phase I, participants will be randomly assigned to receive either rTMS or sham stimulation. The sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. In Phase II, participants who were unresponsive to Phase I treatment will receive daily rTMS at a lower dose for 3 weeks. Participants who show signs of improvement, but have not achieved remission, may continue Phase II for 4 additional weeks. Baseline magnetic resonance images will be used to determine the optimal stimulus intensity by adjusting for individual differences in cortical to skull distances. Phase III participants will be only those who achieved remission in the first 2 phases. These participants will receive antidepressant medication treatment daily for six months. Participants' functional status and symptoms of depression will be measured using self-report scales and video-recorded interviews at study start date and at the end of each treatment phase.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Active prefrontal rTMS phase1 | Experimental | Procedure: Prefrontal rTMSPhase I participants receiving rTMS |
| Sham rTMS phase 1 | Placebo comparator | Procedure: Sham StimulationPhase I participants receiving sham stimulation |
| rTMS extension | Experimental | Procedure: Prefrontal rTMSrTMS. Phase II participants, all of whom did not meet remission requirements after phase 1. They all receive active open label rTMS |
| Open label antidepressant regimen | Experimental | Drug: Antidepressant RegimenAll patients who met remission who were then transitioned to medications after the TMS trial was completed. |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Diagnosis of major depression with a current episode
- Hamilton Rating Scale for Depression score higher than 20
- No response or intolerance to antidepressant medication in the current depressive episode
Key exclusion criteria (4 listed)
- Current use of antidepressants
- Diagnosis of psychosis or anxiety disorder
- Current substance abuse
- Seizures or history of head trauma
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 |
|---|---|---|
| Prefrontal rTMSAlso: TMS, rTMSParticipants receive 120% motor threshold (MT) over left and right prefrontal cortex. Treatments will be administered daily for 3 weeks. Participants who show signs of improvement may continue Phase I for up to 3 additional weeks. | Procedure or surgery | Active prefrontal rTMS phase1, rTMS extension |
| Antidepressant RegimenAlso: medicationParticpants who acheive remission with rTMS may start antidepressant medication in phase III. | Drug | Open label antidepressant regimen |
| Sham StimulationThe sham stimulation will mimic the sensation of rTMS but will not induce an intracerebral current. Treatments will be administered daily for 3 weeks. | Procedure or surgery | Sham rTMS phase 1 |
Primary outcome
Depression Remission, as Measured by the Hamilton Rating Scale for Depression
Time frame: Measured at the end of Phases 1, 2, and 3
The Hamilton Rating Scale for Depression 17-item total score ranges from 0 to 52 with higher scores indicating more depression. Remission is defined as a total score of ≤ 8
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Dec 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23769413Borckardt JJ, Nahas ZH, Teal J, Lisanby SH, McDonald WM, Avery D, Durkalski V, Pavlicova M, Long JM, Sackeim HA, George MS. The painfulness of active, but not sham, transcranial magnetic stimulation decreases rapidly over time: results from the double-blind phase of the OPT-TMS Trial. Brain Stimul. 2013 Nov;6(6):925-8. doi: 10.1016/j.brs.2013.04.009. Epub 2013 May 21.
- Derived from this study: PubMed 20439832George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.
- Individual participant dataSharing planned: Yes. Interested researchers can email the PI, Dr. George, with a request and how they plan to analyze the data. He will then make available a de-identified copy of the data.
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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.
Mark S. George, MD principal investigator
Medical University of South Carolina
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Prefrontal rTMS and Antidepressant Regimen in people with Depression, run by Medical University of South Carolina at 4 sites 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 3 inclusion and 4 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 Dec 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Dec 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?
Depression Remission, as Measured by the Hamilton Rating Scale for Depression (time frame: Measured at the end of Phases 1, 2, and 3). 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 NCT00149838, which also lists 2 linked publications.
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 Dec 2018.