DepressionNCT02685488
Investigating Transcranial Ultrasound as a Potential Intervention for Depression
A study testing Transcranial Ultrasound Power in people with Depression and Anxiety Disorders, run by University of Arizona.
Trial summary
Depression is the leading cause of disability worldwide. Because a significant number of people with depression do not respond to medication or therapy, alternative treatment options are greatly needed. Recent research has focused on brain stimulation methods due to their therapeutic utility for treating depression. Read more about this study
- Who is it for?
- Ages 18 to 35 years
- Conditions the study is for
- Depression, Anxiety Disorders
- What is being tested?
- Transcranial Ultrasound Power
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 26 participants
- Where
- No sites listed yet
- Study dates
- Oct 2015to May 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 18 to 35 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Beck Depression Inventory score between 10 and 25
Who cannot join
- left-handedness
- prior serious head-related injury
- any medical condition that would impact EEG profiles
- chronic migraines or other severe headaches
- pregnancy
- lack of proficiency in English
Show all 9Show fewer
- lack of secure housing
- current confounding treatment (including any psychotropic medication or psychotherapy)
- current active suicidal potential necessitating immediate treatment, as such participants will be referred for immediate treatment.
About this study
Official title: A Pilot Study: Investigating Transcranial Ultrasound as a Potential Intervention for Mild to Moderate Depression
Depression is the leading cause of disability worldwide. Because a significant number of people with depression do not respond to medication or therapy, alternative treatment options are greatly needed. Recent research has focused on brain stimulation methods due to their therapeutic utility for treating depression. Yet, current brain stimulation methods have drawbacks, including invasive surgery and limited precision in targeting specific areas. A novel brain stimulation method, transcranial ultrasound (TUS), is noninvasive, has greater spatial precision than most existing methods, and is proven safe for humans. TUS has been found to increase positive mood in chronic pain patients. In a double blind study, TUS increased positive mood in over 140 healthy undergraduates at the University of Arizona.
Despite evidence that TUS can increase positive mood in humans, it has yet to be investigated whether TUS can increase positive mood in humans who are experiencing chronic low mood or depression. The present study will, for the first time, examine whether TUS can improve depressive symptoms. Twenty to thirty participants with mild to moderate depressive symptoms (Beck Depression Inventory Score between 10 and 25) will be randomly assigned to a TUS sham or TUS activation condition. In the TUS activation condition, TUS will be used to stimulate the right fronto-temporal area, which has previously been shown to increase positive mood. Participants in the TUS sham condition will not receive any brain stimulation. Participants will attend five sessions within seven days or ten sessions within fourteen days. At each session, in addition to brain stimulation, self-reported mood and depressive symptoms will be recorded. Furthermore, the investigators will use electroencephalogram (EEG) to record changes in brain electrical signals during TUS stimulation. Based on prior research, the investigators predict that mood will increase and depressive symptoms will decrease with TUS stimulation.
Read the detailed description
Participants will first complete the online screening and those who qualify to complete the study will be contacted via telephone (see above for telephone recruitment and consent procedure). After providing informed consent, on the first day, participants will be randomly assigned to either a TUS treatment or a TUS sham condition (placebo), and the study will be double blind. Participants in the TUS treatment condition (with sham or treatment unknown to both participant and experimenter) will have TUS stimulation at the right fronto-temporal area five times within seven days or ten times within fourteen days.
Participants will sign up for the first five sessions first but will be reminded participants may withdraw from the study at any time. Should participants choose to continue with the second week of treatment, participants will be scheduled for another five sessions. In other words, participants will have the option of completing 10 days of the procedure. The procedure does not differ between week 1 and week 2. However, participants will be compensated less for week 2. Participants will have the option to continue into week 2, as participants may find that the treatment is benefiting them. The first, fifth, and tenth days of the study will take approximately 2 hours and the second, third, fourth, sixth, seventh, eighth, and ninth will take only one hour.
In the sham condition, the ultrasound probe will be placed at the right fronto-temporal area five times over the course of seven days or ten times over the course of fourteen days without the stimulation. Prior research has shown that stimulation at this area induces positive mood change and is implicated in positive mood. On the first, middle, and last day of the procedure (day 1, 5, 10), EEG data will be collected. On the second, third, and fourth day as well as sixth through ninth days of the procedure EEG data will not be collected and only TUS stimulation will occur. Collecting EEG data at these points will allow for comparison of resting electrical brain profiles from the beginning of the study to the end of the study. Additionally, the investigators will assess state mood and rumination before and after TUS, as well as depressive and anxiety symptoms at the end of each day. The state mood and rumination will allow us to examine the mood effects of TUS, whereas the depressive and anxiety symptoms questionnaires will allow us to examine any changes in these important profiles over the course of the study.
- Conditions
- Depression, Anxiety Disorders
- Being tested
- Transcranial Ultrasound Power, Transcranial Ultrasound Sham
- Medical subject headings
- Depression, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Ultrasound PowerDevice
Transcranial ultrasound will be to stimulate at the right fronto-temporal cortex. 30 seconds of stimulation at 500 kHZ with duty cycle 0.24% and pulse rate frequency at 40 Hz.
Transcranial Ultrasound ShamDevice
Transcranial ultrasound will be used without power for a "sham" condition.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Ultrasound Power | Active comparator | Transcranial Ultrasound Power Receives: Device: Transcranial Ultrasound Power |
| Transcranial Ultrasound Sham | Sham comparator | Transcranial Ultrasound Sham. Unknown to both participants and experimenters, the ultrasound will not stimulate. Receives: Device: Transcranial Ultrasound Sham |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive Symptoms Assessed With the Beck Depression Inventory-II
The Beck Depression Inventory-II (BDI-II) is one of the most widely used self-report measures for assessing depression. It includes 21 self-report items. Scores range from 0 to 63, and higher scores indicate higher levels of depressive symptoms. In this study, the BDI-II was used to monitor depressive symptoms each day. The outcome is the change in BDI-II score as measured by BDI-II on Day 5 minus BDI-II on Day 1.
Measured: Once on day 1 & day 5
Secondary outcomes (3)
Rumination Symptoms Assessed With the Ruminative Responses Scale
The Ruminative Responses scale (RRS) consists of 22 statements. It measures rumination, past-focused repetitive thinking that causes and maintains depression. Participants are asked to rate on a scale of 1 (almost never) to 4 (almost always) how much they think about various things (e.g. "think about how alone you feel" and "think about all your shortcomings, failings, faults, mistakes"). Scores range from 22 to 88 with higher scores indicating more rumination. The RRS was used in this study to measure symptoms of rumination on the first and fifth day of this study. The outcome is the difference from Day 5 to Day 1.
Measured: Once on day 1 & 5
Worry Symptoms Assessed With the Penn State Worry Questionnaire
The PSWQ assesses trait worry, a key component of Generalized Anxiety Disorder. Participants rate themselves on a scale of 1 ("not at all typical of me") to 5 ("very typical of me") for sixteen different statements. Scores range from 16-80, and higher scores reflect higher levels of worry. This scale has been widely used to assess worry and will allow for assessment of worry in the present study (Brown et al., 1992). The PSWQ was used to monitor symptoms of worry on first and fifth day of this study. The outcome measure is difference from Day 5 to Day 1.
Measured: Once on day 1 & day 5
Anxiety Symptoms Assessed With the Overall Anxiety Severity and Impairment Scale
The Overall Anxiety Severity and Impairment Scale (OASIS) assesses severity of anxiety symptoms across anxiety disorders and with subsyndromal symptoms. Participants rate five items on a scale from 0 (indicating no anxiety or impairment) to 4 (indicating severe or extreme anxiety or impairment). Scores range from 0 to 20, with higher scores indicating more severe anxiety and impairment from anxiety (Norman et al., 2006). The OASIS was used to monitor overall severity of anxiety on each day of the study. The outcome measure is difference from Day 5 to Day 1.
Measured: Once on day 1 & day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Feb 2016 (estimated)
- Study startOct 2015
- Primary completionApr 2016
- Study completionMay 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.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John Allen, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02685488
- Sponsor's protocol ID
- RSRCH---703FY'15
- Status last verified
- Jan 2018
- First submitted
- 14 Feb 2016
- Last updated
- 8 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Hameroff S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, Lucas A, Amos Q, Buadu A, Badal JJ. Transcranial ultrasound (TUS) effects on mental states: a pilot study. Brain Stimul. 2013 May;6(3):409-15. doi: 10.1016/j.brs.2012.05.002. Epub 2012 May 29.
PubMed 22664271Tufail Y, Yoshihiro A, Pati S, Li MM, Tyler WJ. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat Protoc. 2011 Sep 1;6(9):1453-70. doi: 10.1038/nprot.2011.371.
PubMed 21886108Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003 Apr 15;53(8):649-59. doi: 10.1016/s0006-3223(03)00231-2.
PubMed 12706951Gavrilov LR, Tsirulnikov EM, Davies IA. Application of focused ultrasound for the stimulation of neural structures. Ultrasound Med Biol. 1996;22(2):179-92. doi: 10.1016/0301-5629(96)83782-3.
PubMed 8735528Bystritsky A, Korb AS, Douglas PK, Cohen MS, Melega WP, Mulgaonkar AP, DeSalles A, Min BK, Yoo SS. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011 Jul;4(3):125-36. doi: 10.1016/j.brs.2011.03.007. Epub 2011 Apr 1.
PubMed 21777872ter Haar G. Therapeutic applications of ultrasound. Prog Biophys Mol Biol. 2007 Jan-Apr;93(1-3):111-29. doi: 10.1016/j.pbiomolbio.2006.07.005. Epub 2006 Aug 4.
PubMed 16930682
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study: Investigating Transcranial Ultrasound as a Potential Intervention for Mild to Moderate Depression
- ClinicalTrials.gov ID
- NCT02685488
- Acronym / sponsor ID
- RSRCH---703FY'15
- Conditions
- Depression, Anxiety Disorders
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Apr 2016 (actual)
- Study completion
- May 2016 (actual)
- First posted
- 18 Feb 2016 (estimated)
- Results
- Posted 8 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Depression is the leading cause of disability worldwide. Because a significant number of people with depression do not respond to medication or therapy, alternative treatment options are greatly needed. Recent research has focused on brain stimulation methods due to their therapeutic utility for treating depression. Yet, current brain stimulation methods have drawbacks, including invasive surgery and limited precision in targeting specific areas. A novel brain stimulation method, transcranial ultrasound (TUS), is noninvasive, has greater spatial precision than most existing methods, and is proven safe for humans. TUS has been found to increase positive mood in chronic pain patients. In a double blind study, TUS increased positive mood in over 140 healthy undergraduates at the University of Arizona.
Despite evidence that TUS can increase positive mood in humans, it has yet to be investigated whether TUS can increase positive mood in humans who are experiencing chronic low mood or depression. The present study will, for the first time, examine whether TUS can improve depressive symptoms. Twenty to thirty participants with mild to moderate depressive symptoms (Beck Depression Inventory Score between 10 and 25) will be randomly assigned to a TUS sham or TUS activation condition. In the TUS activation condition, TUS will be used to stimulate the right fronto-temporal area, which has previously been shown to increase positive mood. Participants in the TUS sham condition will not receive any brain stimulation. Participants will attend five sessions within seven days or ten sessions within fourteen days. At each session, in addition to brain stimulation, self-reported mood and depressive symptoms will be recorded. Furthermore, the investigators will use electroencephalogram (EEG) to record changes in brain electrical signals during TUS stimulation. Based on prior research, the investigators predict that mood will increase and depressive symptoms will decrease with TUS stimulation.
Detailed description
Participants will first complete the online screening and those who qualify to complete the study will be contacted via telephone (see above for telephone recruitment and consent procedure). After providing informed consent, on the first day, participants will be randomly assigned to either a TUS treatment or a TUS sham condition (placebo), and the study will be double blind. Participants in the TUS treatment condition (with sham or treatment unknown to both participant and experimenter) will have TUS stimulation at the right fronto-temporal area five times within seven days or ten times within fourteen days.
Participants will sign up for the first five sessions first but will be reminded participants may withdraw from the study at any time. Should participants choose to continue with the second week of treatment, participants will be scheduled for another five sessions. In other words, participants will have the option of completing 10 days of the procedure. The procedure does not differ between week 1 and week 2. However, participants will be compensated less for week 2. Participants will have the option to continue into week 2, as participants may find that the treatment is benefiting them. The first, fifth, and tenth days of the study will take approximately 2 hours and the second, third, fourth, sixth, seventh, eighth, and ninth will take only one hour.
In the sham condition, the ultrasound probe will be placed at the right fronto-temporal area five times over the course of seven days or ten times over the course of fourteen days without the stimulation. Prior research has shown that stimulation at this area induces positive mood change and is implicated in positive mood. On the first, middle, and last day of the procedure (day 1, 5, 10), EEG data will be collected. On the second, third, and fourth day as well as sixth through ninth days of the procedure EEG data will not be collected and only TUS stimulation will occur. Collecting EEG data at these points will allow for comparison of resting electrical brain profiles from the beginning of the study to the end of the study. Additionally, the investigators will assess state mood and rumination before and after TUS, as well as depressive and anxiety symptoms at the end of each day. The state mood and rumination will allow us to examine the mood effects of TUS, whereas the depressive and anxiety symptoms questionnaires will allow us to examine any changes in these important profiles over the course of the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Transcranial Ultrasound Power | Active comparator | Device: Transcranial Ultrasound PowerTranscranial Ultrasound Power |
| Transcranial Ultrasound Sham | Sham comparator | Device: Transcranial Ultrasound ShamTranscranial Ultrasound Sham. Unknown to both participants and experimenters, the ultrasound will not stimulate. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Beck Depression Inventory score between 10 and 25
Key exclusion criteria (9 listed)
- left-handedness
- prior serious head-related injury
- any medical condition that would impact EEG profiles
- chronic migraines or other severe headaches
- pregnancy
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 |
|---|---|---|
| Transcranial Ultrasound PowerTranscranial ultrasound will be to stimulate at the right fronto-temporal cortex. 30 seconds of stimulation at 500 kHZ with duty cycle 0.24% and pulse rate frequency at 40 Hz. | Device | Transcranial Ultrasound Power |
| Transcranial Ultrasound ShamTranscranial ultrasound will be used without power for a "sham" condition. | Device | Transcranial Ultrasound Sham |
Primary outcome
Depressive Symptoms Assessed With the Beck Depression Inventory-II
Time frame: Once on day 1 & day 5
The Beck Depression Inventory-II (BDI-II) is one of the most widely used self-report measures for assessing depression. It includes 21 self-report items. Scores range from 0 to 63, and higher scores indicate higher levels of depressive symptoms. In this study, the BDI-II was used to monitor depressive symptoms each day. The outcome is the change in BDI-II score as measured by BDI-II on Day 5 minus BDI-II on Day 1.
3 secondary outcomes
Rumination Symptoms Assessed With the Ruminative Responses Scale
Time frame: Once on day 1 & 5
Worry Symptoms Assessed With the Penn State Worry Questionnaire
Time frame: Once on day 1 & day 5
Anxiety Symptoms Assessed With the Overall Anxiety Severity and Impairment Scale
Time frame: Once on day 1 & day 5
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22664271Hameroff S, Trakas M, Duffield C, Annabi E, Gerace MB, Boyle P, Lucas A, Amos Q, Buadu A, Badal JJ. Transcranial ultrasound (TUS) effects on mental states: a pilot study. Brain Stimul. 2013 May;6(3):409-15. doi: 10.1016/j.brs.2012.05.002. Epub 2012 May 29.
- Background: PubMed 21886108Tufail Y, Yoshihiro A, Pati S, Li MM, Tyler WJ. Ultrasonic neuromodulation by brain stimulation with transcranial ultrasound. Nat Protoc. 2011 Sep 1;6(9):1453-70. doi: 10.1038/nprot.2011.371.
- Background: PubMed 12706951Fava M. Diagnosis and definition of treatment-resistant depression. Biol Psychiatry. 2003 Apr 15;53(8):649-59. doi: 10.1016/s0006-3223(03)00231-2.
- Background: PubMed 8735528Gavrilov LR, Tsirulnikov EM, Davies IA. Application of focused ultrasound for the stimulation of neural structures. Ultrasound Med Biol. 1996;22(2):179-92. doi: 10.1016/0301-5629(96)83782-3.
- Background: PubMed 21777872Bystritsky A, Korb AS, Douglas PK, Cohen MS, Melega WP, Mulgaonkar AP, DeSalles A, Min BK, Yoo SS. A review of low-intensity focused ultrasound pulsation. Brain Stimul. 2011 Jul;4(3):125-36. doi: 10.1016/j.brs.2011.03.007. Epub 2011 Apr 1.
- Background: PubMed 16930682ter Haar G. Therapeutic applications of ultrasound. Prog Biophys Mol Biol. 2007 Jan-Apr;93(1-3):111-29. doi: 10.1016/j.pbiomolbio.2006.07.005. Epub 2006 Aug 4.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Ultrasound Power in people with Depression and Anxiety Disorders, run by University of Arizona.
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 1 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 8 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 8 Jan 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?
Depressive Symptoms Assessed With the Beck Depression Inventory-II (time frame: Once on day 1 & day 5). 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 NCT02685488, which also lists 6 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 8 Jan 2018.