Major Depressive DisorderPhase 3NEST-MDDNCT01370733
Synchronized Transcranial Magnetic Stimulation (sTMS) in Major Depressive Disorder
A Phase 3 study testing NEST-1 (NeoSync EEG Synchronized TMS) in people with Major Depressive Disorder, run by Wave Neuroscience at 18 sites in United States.
Trial summary
This study is designed to evaluate the safety and efficacy of synchronized transcranial magnetic stimulation (sTMS) using the NeoSync EEG Synchronized TMS device (NEST) in subjects with Major Depressive Disorder. Read more about this study
- Who is it for?
- Ages 22 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- NEST-1 (NeoSync EEG Synchronized TMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 202 participants
- Where
- 18 sitesUnited States
- Study dates
- May 2012to Sep 2013
- Phase
- Phase 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 22 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects will meet the DSM-IV-TR primary diagnosis of initial or recurrent Major Depressive Disorder by DSM-IV-TR criteria rendered by structured interview using the Mini International Neuropsychiatric Interview (MINI).
- HAM-D17 score >= 17 and Item 1 score greater than or equal to 2.
- Duration of current episode >=8 weeks. The definition of an episode is demarcated by a period of >=2 months when the subject did not meet full criteria for the DSM-IV-TR definition of Major Depressive Episode. Maximum duration of current episode cannot exceed 2 years.
- The baseline EEG is of sufficient duration and quality that it can be processed for quantitative analysis.
- Subjects are willing and able to adhere to the intensive treatment schedule and all required study visits.
Who cannot join
- Subjects are unable or unwilling to give informed consent.
- Diagnosed with the following conditions (current unless otherwise stated):
- Any other current primary Axis I mood, anxiety, or psychotic disorder, including bipolar disorder.
- Depression secondary to a general medical condition, or substance-induced.
- History of substance abuse or dependence within the past 6 months (except nicotine and caffeine).
- Any bipolar disorder or psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features in this or previous episodes.
Show all 47Show fewer
- Eating disorder (current or within the past year).
- Obsessive compulsive disorder (lifetime).
- Post-traumatic stress disorder (current or within the past year).
- ADHD (currently being treated).
- Subjects meeting criteria for Axis II cluster A or B diagnosis based upon DSM-IV TR criteria, which in the judgment of the Investigator may hinder the subjects in completing the procedures required by the study protocol.
- Subjects with a clinically defined neurological disorder including, but not limited to:
- Any condition likely to be associated with increased intracranial pressure.
- Space occupying brain lesion.
- Any history of seizure EXCEPT those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study).
- History of stroke.
- Transient ischemic attack within two years.
- Cerebral aneurysm.
- Dementia.
- Mini Mental Status Exam (MMSE-2) score of =<24.
- Parkinson's disease.
- Huntington's disease.
- Multiple sclerosis.
- Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold. Medications that lower the seizure threshold are included in the Prohibited Concomitant Medication (Section 5.7).
- Subjects who are currently hospitalized due to severity of depression symptoms.
- Subjects with any of the following treatment histories:
- TMS treatment within 6 months prior to the screening visit.
- ECT treatment within 1 year prior to the screening visit.
- Failure to respond to TMS or ECT treatment (i.e., consistent with ATHF confidence level 3 or higher) in this or any previous episode.
- Lifetime history of treatment with Deep Brain Stimulation or Vagus Nerve Stimulation.
- Use of any investigational drug or device within 4 weeks of the randomization visit.
- Subjects who have been treated with fluoxetine within the past four weeks.
- If participating in psychotherapy, must have been in stable treatment for at least 2 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the trial.
- Failure to respond to Monoamine Oxidase Inhibitors (MAOIs) in the current episode.
- Use of any medication(s) listed on the Prohibited Concomitant Medication within 1 week of randomization.
- Subjects are adequately benefiting from current antidepressant medication(s).
- Significant acute suicide risk, defined as:
- Suicide attempt within the previous 6 months that required medical treatment; or
- Greater than or equal to 1 suicide attempts in the past 12 months; or
- Has a clear-cut plan for suicide and states that he/she cannot guarantee that he/she will call his/her regular psychiatrist or the Investigator if the impulse to implement the plan becomes substantial during the study; or
- In the Investigator's opinion, is likely to attempt suicide within the next 6 months.
- Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease.
- Intracranial implant (e.g., aneurysm clips, shunts, stimulators, cochlear implants, stents, or electrodes) or any other metal object within or near the head, excluding the mouth, which cannot be safely removed.
- Clinically significant abnormality or clinically significant unstable medical condition, as indicated by medical history, physical examination, ECG results, or clinical laboratory testing, that in the Investigator's judgment might pose a potential safety risk to the subject or limit interpretation of the trial results, e.g., any uncontrolled thyroid disorders, hepatic, cardiac, pulmonary and renal malfunctioning.
- Women who are currently pregnant or not using a medically acceptable means of birth control and women who are breastfeeding.
- Positive urine drug screen for illicit substances. (A positive urine drug screen at screening may be repeated once prior to randomization).
- Any condition which in the judgment of the Investigator would prevent the subject from completion of the study.
Trial locations and contacts
18 sites in 1 country.
18 sites in 1 country
United States18 sites
Sheppard Pratt Health System
Baltimore, Maryland, 21285
MUSC Institute of Psychiatry, Brain Stimulation Lab
Charleston, South Carolina, 29425
Center for Mood Disorders and Neuromodulation Therapies, UMDNJ-SOM
Cherry Hill, New Jersey, 08003
TMS Specialists Chicago
Chicago, Illinois, 60602
UT Southwestern Medical Center
Dallas, Texas, 75390
Duke University Brain Stimulation and Neurophysiology Center
Durham, North Carolina, 27710
Hartford Hospital Institute of Living
Hartford, Connecticut, 06106
R/D Clinical Research
Lake Jackson, Texas, 77566
UCLA Depression Research & Clinic Program
Los Angeles, California, 90024
Mount Sinai School of Medicine
New York, New York, 10029
University of Nebraska Medical Center
Omaha, Nebraska, 68198
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Mood Disorders Treatment Research Program University of Pittsburgh-Western Psychiatric Institute and Clinic
Pittsburgh, Pennsylvania, 15213
Butler Hospital Mood Disorders Research Program, Brown Department of Psychiatry and Human Behavior
Providence, Rhode Island, 02906
UCSD Medical Center
San Diego, California, 92103
Washington University School of Medicine
St Louis, Missouri, 63110
UCLA-Harbor
Torrance, California, 90509
Wake Forest University Medical Center
Winston-Salem, North Carolina, 27157
About this study
Official title: Evaluation of Low Emission NeoSync EEG Synchronized TMS Technology for the Treatment of Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Sham-Controlled, Trial
This study is designed to evaluate the safety and efficacy of synchronized transcranial magnetic stimulation (sTMS) using the NeoSync EEG Synchronized TMS device (NEST) in subjects with Major Depressive Disorder. This is a multicenter study in which subjects will be randomized to receive treatment 5 days per week for 6 weeks. Subjects who complete 6 weeks of double-blind treatment may be eligible to receive up to four weeks of open label sTMS therapy or antidepressant medications during the follow-up phase of the study. Follow-up evaluation visits will be conducted during those four weeks, with the frequency of the visits determined by the treatment choice during that timeframe.
Read the detailed description
Major Depressive Disorder (MDD) is a mental disorder associated with significant functional impairment and disability. Affected individuals present with depressed mood, loss of interest or pleasure, feelings of guilt, low self-worth, disturbed sleep or appetite, low energy, and poor concentration.
Psychopharmacological therapy as today's mainstream treatment has revolutionized the clinical management for major depressive disorders and has been shown to improve the quality of life for many patients. With that, these therapies are not effective for all patients. Results released from the Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D), conducted by the National Institute of Mental Health (NIMH), show that approximately 30% of depressed subjects respond to an SSRI in their first trial, despite adequate dosing and duration of treatment. The SSRI antidepressants do have a more favorable side effect profile than older medications, but they still may be difficult for some patients to tolerate because of gastrointestinal distress, anxiety, insomnia, and sexual dysfunction.
In addition to the psychopharmacologic treatments for depression, other therapies such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) have been shown to have a therapeutic effect in MDD. ECT induces seizures electrically in anesthetized subjects. It is generally safe and effective; however the procedure can have the negative side effect of memory loss and confusion. Treatment with repetitive stimulation (rTMS) is intended to stimulate groups of cells in areas of the brain linked to MDD. While the therapy is non-invasive, it is expensive, involves a complex method for locating the point of stimulation in the brain, and has the potential for seizures.
rTMS uses magnetic pulses which causes neuronal activation of specific areas in the brain. It is generally believed that this activation causes resetting of cortical oscillators to create a therapeutic effect in MDD. The investigators hypothesize that TMS using low energy, sinusoidal magnetic fields synchronized to a patient's individual alpha frequency,(sTMS), can also affect neuronal activity leading to a reemergence of intrinsic rhythms and clinical improvement in MDD. Preliminary study results using sTMS have shown improvements in depressive symptoms with minimal side effects.
This multicenter study is designed to evaluate the safety and efficacy of sTMS in subjects with Major Depressive Disorder. Subjects will be randomized to receive treatment 5 days per week for 6 weeks. At the end of Treatment Week 6, subject will have completed the study treatments and will be offered open label sTMS therapy or alternate antidepressant treatment as clinically indicated. At minimum, subjects will be asked to return for one follow-up visit four weeks after their last double-blind treatment (Week 10) for evaluation and study completion.
- Conditions
- Major Depressive Disorder
- Being tested
- NEST-1 (NeoSync EEG Synchronized TMS), SHAM
- Keywords
- TMS,, MDD,, Depression,, sTMS,, NEST,, NeoSync,, EEG,, synchronous,, non-invasive neuromodulation,, transcranial magnetic stimulation,, antidepressant,
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NEST-1 (NeoSync EEG Synchronized TMS)Device
The NeoSync EEG Synchronized TMS (NEST) is an electromechanical medical device that produces and delivers a sinusoidal magnetic field to areas of the brain in the treatment of Major Depressive Disorder.
SHAMDevice
The sham device is configured to simulate the actual NEST-1 device without sTMS therapy being actively delivered.
| Study group | Role | What they receive |
|---|---|---|
| Active sTMS | Experimental | Treatment with the NEST-1 Device Receives: Device: NEST-1 (NeoSync EEG Synchronized TMS) |
| Sham | Sham comparator | Treatment with a sham (inactive) device, identical in sound and appearance to the NEST-1 Device Receives: Device: SHAM |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean HAM-D17 Total Score Change (Intent to Treat - All)
The mean HAM-D17 total score change from Baseline (Day 0) to Week 6 compared between the active treatment and sham-controlled groups. If any subject did not complete the double-blind phase in the ITT population, the assessment last observation carried forward (LOCF) was used. The single value provided in each arm reflects the change seen.
For this trial, the Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset of the HAM-D28, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. The HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. A reduction of 50% or more in total score from Baseline indicates clinical response.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Mean HAM-D17 Total Score Change (Per Protocol - All)
The mean HAM-D17 total score change from Baseline (Day 0) to Week 6 compared between the active treatment and sham-controlled groups. All subjects in the Per Protocol analysis completed Week 6. Baseline HAM-D17 total score was directly compared to the HAM-D17 total score at Week 6. The single value provided in each arm reflects the change seen.
For this trial, the Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset of the HAM-D28, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. The HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. A reduction of 50% or more in total score from Baseline indicates clinical response.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Secondary outcomes (7)
Mean HAM-D17 Total Score Change (Per Protocol - Non-Naive Subjects)
All subjects in the Per Protocol analysis completed Week 6. Baseline HAM-D17 total score was directly compared to Week 6 HAM-D17 total score. The single value provided in each arm reflects this change.
This analysis included only Per Protocol subjects exposed to an antidepressant medication in their current episode (non-naive). This includes past history of intolerance, resistance, or inadequate dosing/duration.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset of the HAM-D28, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. The HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. A reduction of 50% or more in total score from Baseline indicates clinical response.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Response at Week 6 or Early Termination (Intent to Treat)
For this outcome, the Hamilton Rating Scale for Depression (HAM-D17) was utilized to determine clinical response. Response is defined as a reduction of at least 50% in total HAM-D17 score from Baseline through Week 6. If any subject did not complete the double-blind phase (Week 6) in the ITT population, the assessment last observation carried forward (LOCF) was used.
This outcome provides the total number of subjects in each arm that achieved clinical response within the Intent to Treat population.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Response at Week 6 (Per Protocol - All)
For this outcome, the Hamilton Rating Scale for Depression (HAM-D17) was utilized to determine clinical response. Response is defined as a reduction of at least 50% in total HAM-D17 score from Baseline through Week 6. All subjects in the Per Protocol population completed Week 6.
This outcome provides the total number of subjects in each arm that achieved clinical response within the Per Protocol population.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Response at Week 6 (Per Protocol - Non-Naive Subjects)
The Hamilton Rating Scale for Depression (HAM-D17) was utilized to determine clinical response, defined as a reduction of at least 50% in total HAM-D17 score from Baseline through Week 6. All subjects in the Per Protocol (PP) population completed Week 6. This analysis includes only PP subjects exposed to an antidepressant medication in their current episode (non-naive).
This outcome provides the total number of subjects in each arm that achieved clinical response within the Non-Naive, Per Protocol population.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Remission at Week 6 or Early Termination (Intent to Treat)
The Hamilton Rating Scale for Depression (HAM-D17) was utilized to determine clinical remission. Remission is defined as a total HAM-D17 score ≤ 7. If any subject did not complete the double-blind phase (Week 6) in the Intent to Treat (ITT) population, the assessment last observation carried forward (LOCF) was used.
This outcome provides the total number of subjects in each arm that achieved clinical remission within the ITT population.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Remission at Week 6 (Per Protocol - All)
For this outcome, the Hamilton Rating Scale for Depression (HAM-D17) was utilized to determine clinical remission. Remission is defined as a total HAM-D17 score ≤ 7. All subjects in the Per Protocol population completed Week 6.
This outcome provides the total number of subjects in each arm that achieved clinical remission within the Per Protocol population at Week 6.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity.
Measured: Baseline to End of Double-Blind Treatment Period (up to week 6)
Number of Subjects Who Demonstrate Clinical Remission at Week 6 or Early Termination (Per Protocol - Non-Naive Subjects)
The Hamilton Rating Scale for Depression (HAM-D17) was utilized to determine clinical remission. Remission is defined as a total HAM-D17 score ≤ 7. All subjects in the Per Protocol population completed Week 6. This analysis includes only PP subjects exposed to an antidepressant medication in their current episode (non-naive).
This outcome provides the total number of subjects in each arm that achieved clinical remission at Week 6 within the Non-Naive, Per Protocol population.
The Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity.
Measured: Baseline to End of Double-Blind Treatment Period (Week 6)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2011 (estimated)
- Study startMay 2012
- Primary completionAug 2013
- Study completionSep 2013
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 (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 202 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wave Neuroscience
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andrew Leuchter, MD, Principal investigator, UCLA Depression Research & Clinic Program
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01370733
- Sponsor's protocol ID
- NND3001
- Acronym
- NEST-MDD
- Status last verified
- Oct 2015
- First submitted
- 8 Jun 2011
- Last updated
- 26 Oct 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Leuchter AF, Cook IA, Feifel D, Goethe JW, Husain M, Carpenter LL, Thase ME, Krystal AD, Philip NS, Bhati MT, Burke WJ, Howland RH, Sheline YI, Aaronson ST, Iosifescu DV, O'Reardon JP, Gilmer WS, Jain R, Burgoyne KS, Phillips B, Manberg PJ, Massaro J, Hunter AM, Lisanby SH, George MS. Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression. Brain Stimul. 2015 Jul-Aug;8(4):787-94. doi: 10.1016/j.brs.2015.05.005. Epub 2015 May 22.
PubMed 26143022
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of Low Emission NeoSync EEG Synchronized TMS Technology for the Treatment of Major Depressive Disorder: A Multicenter, Randomized, Double-Blind, Sham-Controlled, Trial
- ClinicalTrials.gov ID
- NCT01370733
- Acronym / sponsor ID
- NEST-MDD / NND3001
- Conditions
- Major Depressive Disorder
- Keywords
- TMS,, MDD,, Depression,, sTMS,, NEST,, NeoSync,, EEG,, synchronous,
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 202 participants (actual)
- Lead sponsor
- Wave NeuroscienceIndustry (pharma, biotech, devices)
- Study start
- May 2012
- Primary completion
- Aug 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 10 Jun 2011 (estimated)
- Results
- Posted 14 Jul 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to evaluate the safety and efficacy of synchronized transcranial magnetic stimulation (sTMS) using the NeoSync EEG Synchronized TMS device (NEST) in subjects with Major Depressive Disorder. This is a multicenter study in which subjects will be randomized to receive treatment 5 days per week for 6 weeks. Subjects who complete 6 weeks of double-blind treatment may be eligible to receive up to four weeks of open label sTMS therapy or antidepressant medications during the follow-up phase of the study. Follow-up evaluation visits will be conducted during those four weeks, with the frequency of the visits determined by the treatment choice during that timeframe.
Detailed description
Major Depressive Disorder (MDD) is a mental disorder associated with significant functional impairment and disability. Affected individuals present with depressed mood, loss of interest or pleasure, feelings of guilt, low self-worth, disturbed sleep or appetite, low energy, and poor concentration.
Psychopharmacological therapy as today's mainstream treatment has revolutionized the clinical management for major depressive disorders and has been shown to improve the quality of life for many patients. With that, these therapies are not effective for all patients. Results released from the Sequenced Treatment Alternatives to Relieve Depression Study (STAR*D), conducted by the National Institute of Mental Health (NIMH), show that approximately 30% of depressed subjects respond to an SSRI in their first trial, despite adequate dosing and duration of treatment. The SSRI antidepressants do have a more favorable side effect profile than older medications, but they still may be difficult for some patients to tolerate because of gastrointestinal distress, anxiety, insomnia, and sexual dysfunction.
In addition to the psychopharmacologic treatments for depression, other therapies such as electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) have been shown to have a therapeutic effect in MDD. ECT induces seizures electrically in anesthetized subjects. It is generally safe and effective; however the procedure can have the negative side effect of memory loss and confusion. Treatment with repetitive stimulation (rTMS) is intended to stimulate groups of cells in areas of the brain linked to MDD. While the therapy is non-invasive, it is expensive, involves a complex method for locating the point of stimulation in the brain, and has the potential for seizures.
rTMS uses magnetic pulses which causes neuronal activation of specific areas in the brain. It is generally believed that this activation causes resetting of cortical oscillators to create a therapeutic effect in MDD. The investigators hypothesize that TMS using low energy, sinusoidal magnetic fields synchronized to a patient's individual alpha frequency,(sTMS), can also affect neuronal activity leading to a reemergence of intrinsic rhythms and clinical improvement in MDD. Preliminary study results using sTMS have shown improvements in depressive symptoms with minimal side effects.
This multicenter study is designed to evaluate the safety and efficacy of sTMS in subjects with Major Depressive Disorder. Subjects will be randomized to receive treatment 5 days per week for 6 weeks. At the end of Treatment Week 6, subject will have completed the study treatments and will be offered open label sTMS therapy or alternate antidepressant treatment as clinically indicated. At minimum, subjects will be asked to return for one follow-up visit four weeks after their last double-blind treatment (Week 10) for evaluation and study completion.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active sTMS | Experimental | Device: NEST-1 (NeoSync EEG Synchronized TMS)Treatment with the NEST-1 Device |
| Sham | Sham comparator | Device: SHAMTreatment with a sham (inactive) device, identical in sound and appearance to the NEST-1 Device |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subjects will meet the DSM-IV-TR primary diagnosis of initial or recurrent Major Depressive Disorder by DSM-IV-TR criteria rendered by structured interview using the Mini International Neuropsychiatric Interview (MINI).
- HAM-D17 score >= 17 and Item 1 score greater than or equal to 2.
- Duration of current episode >=8 weeks. The definition of an episode is demarcated by a period of >=2 months when the subject did not meet full criteria for the DSM-IV-TR definition of Major Depressive Episode. Maximum duration of current episode cannot exceed 2 years.
- The baseline EEG is of sufficient duration and quality that it can be processed for quantitative analysis.
- Subjects are willing and able to adhere to the intensive treatment schedule and all required study visits.
Key exclusion criteria (47 listed)
- Subjects are unable or unwilling to give informed consent.
- Diagnosed with the following conditions (current unless otherwise stated):
- Subjects meeting criteria for Axis II cluster A or B diagnosis based upon DSM-IV TR criteria, which in the judgment of the Investigator may hinder the subjects in completing the procedures required by the study protocol.
- Subjects with a clinically defined neurological disorder including, but not limited to:
- Subjects who are currently hospitalized due to severity of depression symptoms.
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 |
|---|---|---|
| NEST-1 (NeoSync EEG Synchronized TMS)The NeoSync EEG Synchronized TMS (NEST) is an electromechanical medical device that produces and delivers a sinusoidal magnetic field to areas of the brain in the treatment of Major Depressive Disorder. | Device | Active sTMS |
| SHAMThe sham device is configured to simulate the actual NEST-1 device without sTMS therapy being actively delivered. | Device | Sham |
Primary outcome
Mean HAM-D17 Total Score Change (Intent to Treat - All)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
The mean HAM-D17 total score change from Baseline (Day 0) to Week 6 compared between the active treatment and sham-controlled groups. If any subject did not complete the double-blind phase in the ITT population, the assessment last observation carried forward (LOCF) was used. The single value provided in each arm reflects the change seen. For this trial, the Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset of the HAM-D28, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. The HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. A reduction of 50% or more in total score from Baseline indicates clinical response.
Mean HAM-D17 Total Score Change (Per Protocol - All)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
The mean HAM-D17 total score change from Baseline (Day 0) to Week 6 compared between the active treatment and sham-controlled groups. All subjects in the Per Protocol analysis completed Week 6. Baseline HAM-D17 total score was directly compared to the HAM-D17 total score at Week 6. The single value provided in each arm reflects the change seen. For this trial, the Hamilton Rating Scale for Depression (HAM-D28) was performed as a baseline assessment. A subset of the HAM-D28, the HAM-D17, was utilized as both a baseline and efficacy measure. It's considered the gold standard for rating depression severity and used frequently in clinical trials. The HAM-D17 score ranges from 0-52; a score of 0-7 is generally accepted to be within the normal range (or in clinical remission), while a score of 20 or higher indicates at least moderate severity. A reduction of 50% or more in total score from Baseline indicates clinical response.
7 secondary outcomes
Mean HAM-D17 Total Score Change (Per Protocol - Non-Naive Subjects)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Response at Week 6 or Early Termination (Intent to Treat)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Response at Week 6 (Per Protocol - All)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Response at Week 6 (Per Protocol - Non-Naive Subjects)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Remission at Week 6 or Early Termination (Intent to Treat)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
Number of Subjects Who Demonstrate Clinical Remission at Week 6 (Per Protocol - All)
Time frame: Baseline to End of Double-Blind Treatment Period (up to week 6)
Number of Subjects Who Demonstrate Clinical Remission at Week 6 or Early Termination (Per Protocol - Non-Naive Subjects)
Time frame: Baseline to End of Double-Blind Treatment Period (Week 6)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 26143022Leuchter AF, Cook IA, Feifel D, Goethe JW, Husain M, Carpenter LL, Thase ME, Krystal AD, Philip NS, Bhati MT, Burke WJ, Howland RH, Sheline YI, Aaronson ST, Iosifescu DV, O'Reardon JP, Gilmer WS, Jain R, Burgoyne KS, Phillips B, Manberg PJ, Massaro J, Hunter AM, Lisanby SH, George MS. Efficacy and Safety of Low-field Synchronized Transcranial Magnetic Stimulation (sTMS) for Treatment of Major Depression. Brain Stimul. 2015 Jul-Aug;8(4):787-94. doi: 10.1016/j.brs.2015.05.005. Epub 2015 May 22.
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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.
Andrew Leuchter, MD principal investigator
UCLA Depression Research & Clinic Program
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing NEST-1 (NeoSync EEG Synchronized TMS) in people with Major Depressive Disorder, run by Wave Neuroscience at 18 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 5 inclusion and 47 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 26 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 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 phase mean?
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 14 Jul 2015). 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?
Mean HAM-D17 Total Score Change (Intent to Treat - All) (time frame: Baseline to End of Double-Blind Treatment Period (Week 6)). The study lists 2 primary outcomes in all. 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 NCT01370733, 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 26 Oct 2015.