Treatment Resistant DepressionNCT01435148
Deep Brain Stimulation in Treatment Resistant Depression
A study testing Deep Brain Stimulation, implanted in people with Treatment Resistant Depression, run by North Bristol NHS Trust at 1 site in United Kingdom.
Trial summary
Recurrent major depressive disorder affects about 3-5% of the population. It is anticipated that by 2020, depression will be the most common cause of disability worldwide in the 18-55 age group. About two-thirds of these patients respond to first-line treatment (antidepressants). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Deep Brain Stimulation, implanted
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2006to Dec 2012
- Phase
- Interventional
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who have major depressive disorder (according to the Diagnostic and Statistical Manual version IV) and who:
- Do not respond or have ceased to respond to treatment including:
- Cognitive Behaviour Therapy (CBT) or other validated psychotherapy.
- Antidepressants from three different classes in BNF or maximum tolerated (if lower than BNF) doses
- Lithium augmentation
- 2 courses of ECT (or only respond to "maintenance" ECT)(lack of response in previous episodes and unwillingness to try again will also count).
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- Consent to take part in the trial
- Are physically fit
- Have no suicidal intent
- Have no history of hypomania, mania or psychosis
- Montgomery Asberg Depression Rating Scale score > 21
Who cannot join
- Patients with a history of continuous depression from late teens or early twenties without clear response to treatments or without periods of spontaneous remission,
- Pregnancy
- History of significant head trauma
- Dementia
- Cerebral infarcts
- Poor physical health
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- No capacity to consent
- Inability to carry out research protocol
- Mood incongruent psychotic phenomena or drug or alcohol addiction. In addition patients will be excluded if detained under the Mental Health Act.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Neurosurgey Department, Frenchay Hospital
Bristol, Bristol, BS16 1LE
About this study
Official title: A Double Blind Randomised Pilot Study of Deep Brain Stimulation in Patients With Treatment Resistant Unipolar Major Depressive Disorder.
Recurrent major depressive disorder affects about 3-5% of the population. It is anticipated that by 2020, depression will be the most common cause of disability worldwide in the 18-55 age group. About two-thirds of these patients respond to first-line treatment (antidepressants). In addition, prolonged administration of antidepressants in patients who respond results in remission in 80% of patients per year. However, a significant proportion of patients either fail to respond in spite of determined pharmacological treatments, electroconvulsive therapy and other treatments or do not achieve sustained remission. The personal, psychiatric, medical, social and economic consequences are devastating for these, treatment resistant, patients. This investigation aims to evaluate the feasibility of deep brain stimulation in patients with treatment resistant depression as a viable alternative to ablative neurosurgery.The hypothesis is that some patients will respond to stimulation in one site rather than the other and that some patients will respond to double rather than single site stimulation.
Read the detailed description
Patients will be selected according to inclusion/ exclusion criteria after referral from their psychiatric team or, in exceptional cases, from their GP. Patients will be referred to the trial after being assessed by Dr Malizia (Consultant Senior Lecturer) in the Treatment Resistant Disorders Psychopharmacology clinic in the Bristol Royal Infirmary. Informed written consent and baseline measures will be taken for all patients.
We plan to recruit 8 patients with treatment resistant unipolar depression for a single blind trial of bilateral consecutive deep brain stimulation of Cg25 and ventral anterior capsule separately and then together. Medication will be left unchanged and maintained to the same level until the end of the study postoperatively. However, medication thought to be potentially detrimental in the long term will be stopped or reduced prior to surgery and a period of at least 6 weeks stability in prescribed medication will be required prior to baseline assessment.
The surgical procedure will be under general anaesthesia and will consist of implanting bilateral deep brain stimulating electrodes (four overall) into Brodmann's area 25 and the nucleus accumbens/ ventral anterior capsule. Following the operation a period of one-week recovery will be allowed to minimise any effect secondary to target impact effect at surgery or from post-operative oedema.
After recovery the combination of electrodes with maximal response will be assessed in a double blind design (patient and raters).
Stimulation will be bilateral. Four patients will be randomised to receive Cg25 stimulation first and 4 patients will be randomised to receive anterior capsule/ventral striatal stimulation first. Patients will be blind to the order of stimulation, to the contacts selected and to any 'off' period in the contact selection process.
After at least four months patients will crossover to the alternative site of stimulation unless they have achieved remission (MADRS <8 for at least two months). Patients and raters will still be blind to the site of stimulation. After a further four months selection will be for both sets of contacts that have achieved best results. If the MADRS score is <8 with one location and no significant improvement has occurred in the other (MADRS>18 and improvement <25%), then only one set of contacts will be stimulated from there on.
Clinical assessments will be at least two monthly on average.
The full evaluation procedure will last an average of 18 months from surgical implantation of the electrodes.
- Conditions
- Treatment Resistant Depression
- Being tested
- Deep Brain Stimulation, implanted
- Keywords
- Deep Brain Stimulation, Treatment Resistant Depression
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deep Brain Stimulation, implantedProcedure or surgery
Deep brain stimulator implanted during neurosurgery. Specific stimulation parameters programmed after surgery as required. After blinded study arms open stimulation of either or both targets.
| Study group | Role | What they receive |
|---|---|---|
| Stimulation of SGC then VACNAC targets | Experimental | Stimulation of the subgenual cingulate cortex (SGC) target will take place first, followed by stimulation of the ventral anterior capsule nucleus accumbens target (VACNAC) if no clinical response after a minimum of 4 months. Receives: Procedure: Deep Brain Stimulation, implanted |
| Stimulation of VACNAC then SGC targets. | Experimental | Stimulation of the ventral anterior capsule nucleus accumbens target (VACNAC) will take place first, followed by stimulation of the subgenual cingulate cortex target (SGC) if no clinical response after a minimum of 4 months. Receives: Procedure: Deep Brain Stimulation, implanted |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in Montgomery and Asberg Rating Scale score of at least 50% at an average of 18 months after implantation.
MADRS is a standard depression rating scale for major depressive disorder over time
Measured: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation.
Secondary outcomes (3)
Clinical Global Impression Improvement Scale(CGI-I). Score <4.
The Clinical Global Impression Scale (CGI) will be used to asses global functioning over time in our patients and will be completed by the interviewing psychiatrist.
Measured: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
Global Assessment of Functioning scale, an improvement of >1/2(100-initial score)
The Global Assessment of Functioning scale is a standardized scale used to asses functioning in patients with chronic conditions. It is useful here as it allows an aspect of 'social' functioning to be assessed during the study. It will be completed by the interviewing psychiatrist.
Measured: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
A decrease of 50% in Hamilton Depression Rating Scale (17 items) at End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
Ham_D is a standard observer rated measure of depression in major depressive disorder over time
Measured: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2011 (estimated)
- Study startDec 2006
- Primary completionDec 2012 (estimated)
- Study completionDec 2012 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- North Bristol NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bristol
- Responsible party
- Principal investigator, Dr Andrea Malizia, North Bristol NHS Trust
- Investigators
- Andrea Malizia, MD, PhD, Principal investigator, Bristol University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01435148
- Sponsor's protocol ID
- 1759
- Other IDs
- 06/Q2001/189
- Status last verified
- Sep 2011
- First submitted
- 2 Sep 2011
- Last updated
- 15 Sep 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double Blind Randomised Pilot Study of Deep Brain Stimulation in Patients With Treatment Resistant Unipolar Major Depressive Disorder.
- ClinicalTrials.gov ID
- NCT01435148
- Acronym / sponsor ID
- 1759
- Conditions
- Treatment Resistant Depression
- Keywords
- Deep Brain Stimulation, Treatment Resistant Depression
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 8 participants (actual)
- Lead sponsor
- North Bristol NHS TrustUniversity, hospital or other
- Collaborators
- University of Bristol
- Study start
- Dec 2006
- Primary completion
- Dec 2012 (estimated)
- Study completion
- Dec 2012 (estimated)
- First posted
- 15 Sep 2011 (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.
Recurrent major depressive disorder affects about 3-5% of the population. It is anticipated that by 2020, depression will be the most common cause of disability worldwide in the 18-55 age group. About two-thirds of these patients respond to first-line treatment (antidepressants). In addition, prolonged administration of antidepressants in patients who respond results in remission in 80% of patients per year. However, a significant proportion of patients either fail to respond in spite of determined pharmacological treatments, electroconvulsive therapy and other treatments or do not achieve sustained remission. The personal, psychiatric, medical, social and economic consequences are devastating for these, treatment resistant, patients. This investigation aims to evaluate the feasibility of deep brain stimulation in patients with treatment resistant depression as a viable alternative to ablative neurosurgery.The hypothesis is that some patients will respond to stimulation in one site rather than the other and that some patients will respond to double rather than single site stimulation.
Detailed description
Patients will be selected according to inclusion/ exclusion criteria after referral from their psychiatric team or, in exceptional cases, from their GP. Patients will be referred to the trial after being assessed by Dr Malizia (Consultant Senior Lecturer) in the Treatment Resistant Disorders Psychopharmacology clinic in the Bristol Royal Infirmary. Informed written consent and baseline measures will be taken for all patients.
We plan to recruit 8 patients with treatment resistant unipolar depression for a single blind trial of bilateral consecutive deep brain stimulation of Cg25 and ventral anterior capsule separately and then together. Medication will be left unchanged and maintained to the same level until the end of the study postoperatively. However, medication thought to be potentially detrimental in the long term will be stopped or reduced prior to surgery and a period of at least 6 weeks stability in prescribed medication will be required prior to baseline assessment.
The surgical procedure will be under general anaesthesia and will consist of implanting bilateral deep brain stimulating electrodes (four overall) into Brodmann's area 25 and the nucleus accumbens/ ventral anterior capsule. Following the operation a period of one-week recovery will be allowed to minimise any effect secondary to target impact effect at surgery or from post-operative oedema.
After recovery the combination of electrodes with maximal response will be assessed in a double blind design (patient and raters).
Stimulation will be bilateral. Four patients will be randomised to receive Cg25 stimulation first and 4 patients will be randomised to receive anterior capsule/ventral striatal stimulation first. Patients will be blind to the order of stimulation, to the contacts selected and to any 'off' period in the contact selection process.
After at least four months patients will crossover to the alternative site of stimulation unless they have achieved remission (MADRS <8 for at least two months). Patients and raters will still be blind to the site of stimulation. After a further four months selection will be for both sets of contacts that have achieved best results. If the MADRS score is <8 with one location and no significant improvement has occurred in the other (MADRS>18 and improvement <25%), then only one set of contacts will be stimulated from there on.
Clinical assessments will be at least two monthly on average.
The full evaluation procedure will last an average of 18 months from surgical implantation of the electrodes.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Stimulation of SGC then VACNAC targets | Experimental | Procedure: Deep Brain Stimulation, implantedStimulation of the subgenual cingulate cortex (SGC) target will take place first, followed by stimulation of the ventral anterior capsule nucleus accumbens target (VACNAC) if no clinical response after a minimum of 4 months. |
| Stimulation of VACNAC then SGC targets. | Experimental | Procedure: Deep Brain Stimulation, implantedStimulation of the ventral anterior capsule nucleus accumbens target (VACNAC) will take place first, followed by stimulation of the subgenual cingulate cortex target (SGC) if no clinical response after a minimum of 4 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients who have major depressive disorder (according to the Diagnostic and Statistical Manual version IV) and who:
- Do not respond or have ceased to respond to treatment including:
- Consent to take part in the trial
- Are physically fit
- Have no suicidal intent
Key exclusion criteria (9 listed)
- Patients with a history of continuous depression from late teens or early twenties without clear response to treatments or without periods of spontaneous remission,
- Pregnancy
- History of significant head trauma
- Dementia
- Cerebral infarcts
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 Stimulation, implantedDeep brain stimulator implanted during neurosurgery. Specific stimulation parameters programmed after surgery as required. After blinded study arms open stimulation of either or both targets. | Procedure or surgery | Stimulation of SGC then VACNAC targets, Stimulation of VACNAC then SGC targets. |
Primary outcome
Decrease in Montgomery and Asberg Rating Scale score of at least 50% at an average of 18 months after implantation.
Time frame: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation.
MADRS is a standard depression rating scale for major depressive disorder over time
3 secondary outcomes
Clinical Global Impression Improvement Scale(CGI-I). Score <4.
Time frame: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
Global Assessment of Functioning scale, an improvement of >1/2(100-initial score)
Time frame: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
A decrease of 50% in Hamilton Depression Rating Scale (17 items) at End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
Time frame: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2011.
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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.
Andrea Malizia, MD, PhD principal investigator
Bristol University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Deep Brain Stimulation, implanted in people with Treatment Resistant Depression, run by North Bristol NHS Trust at 1 site in United Kingdom.
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 11 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: status not confirmed, as of the sponsor's last update on 15 Sep 2011. 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 Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
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?
Decrease in Montgomery and Asberg Rating Scale score of at least 50% at an average of 18 months after implantation. (time frame: End of contact selection and adjustment plus 6 months. An average of 18 months after implantation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2011.