Treatment Resistant DepressionPhase 2NCT03290963
Effect of Lithium Versus Placebo in Adults With Treatment-Resistant Depression Who Are Receiving Ketamine
A Phase 2 study testing Lithium and Ketamine in people with Treatment Resistant Depression, run by William V. Bobo, M.D. at 1 site in United States.
Trial summary
The purpose of this research study is to compare the antidepressant effect of lithium versus placebo in adults receiving ketamine. Lithium is available commercially for depression; ketamine is available commercially and can help the symptoms of depression; however, it has not been approved by the U.S. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Lithium and Ketamine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Nov 2017to Dec 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Ability to provide informed consent;
- Current psychiatric inpatient (voluntary only) or outpatient treatment;
- Meets Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder;
- 9-item Patient Health Questionnaire (PHQ-9) total score > 15 at screening and at baseline (just prior to first acute phase ketamine infusion);
- Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode. Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT);
- Adequate social support, defined as having at least one individual identified who is committed to function as support, including providing transportation to and from outpatient ketamine infusion visits;
- Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.
Who cannot join
- Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms;
- On active lithium treatment;
- Serious risk for suicide, as assessed by the evaluating study clinician; a serious suicide risk will be considered: (a) an inability to control suicide impulses or imminent or unacceptably high risk of suicide in the investigator's judgment; or (b) a recent history of suicidal behavior, which is defined as either one or more suicide attempts (or interrupted suicide attempts) in the 12 months before study entry; or (c) history of serious suicidal behavior, defined as one or more suicide attempts (or interrupted attempts) in the last 3 years with a potential lethality judged by the evaluating study clinician to have possibly resulted in serious injury or death;
- Ongoing prescription of > 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;
- Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression;
- Any active or unstable medical condition judged by the study psychiatrist as conferring too great a level of medical risk to allow inclusion in the study;
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- Use or abuse of methamphetamine, cocaine, cannabis, or stimulants (prescribed and illicit) within the past 12 months;
- Any current abuse or dependence of alcohol or drugs (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their drug or alcohol abuse/dependence is in complete (not partial) and sustained (> 1 year) remission;
- History of traumatic brain injury that resulted in loss of consciousness;
- Developmental delay, mental retardation, or intellectual disorder;
- Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months;
- Cognitive disorder (mild and major categories, per DSM-5);
- Prior participation in another study of ketamine for depression within the prior 6 months;
- History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered for treating symptoms of depression;
- History of hypothyroidism unless taking a stable dose of thyroid medication and asymptomatic for 6 months;
- Significant unstable medical condition
- Hepatic insufficiency (2.5 X Upper Limit of Normal (ULN) for Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT)) within 1 year of consent, past liver transplant recipient, and/or clinical diagnosis of cirrhosis of the liver;
- History of either poor antidepressive response to or poor tolerability of ketamine (any route of administration) when previously administered for treating symptoms of depression;
- History of medical condition(s) which are not recommended to be taken concurrently with lithium; Current anti-depressive pharmacotherapies will not be allowed during the acute phase KET infusions.
- Pregnancy, or nursing;
- Prisoners;
- Involuntary psychiatric hospitalization.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
About this study
Official title: Targeting mTOR/GSK3 With Lithium Augmentation to Enhance and Sustain Rapid Antidepressant Actions of Ketamine in Adults With Treatment-Resistant Depression: A Precision Medicine Approach for Psychiatry
The purpose of this research study is to compare the antidepressant effect of lithium versus placebo in adults receiving ketamine. Lithium is available commercially for depression; ketamine is available commercially and can help the symptoms of depression; however, it has not been approved by the U.S. Food and Drug Administration (FDA) for this use. The FDA has allowed the use of this drug in this research study.
Read the detailed description
This is a randomized clinical trial in adults with Treatment-Resistant Depression. All participants will receive three intravenous (IV) Ketamine (KET) infusions over 7 days. Before receiving the first KET infusion, subjects will be randomized to 2 weeks of pre-KET treatment with either Lithium or matching placebo. Pre-treatment medications will then be continued in a double-blind manner during the acute phase administration of ketamine. Questionnaires will be administered at baseline, prior to each KET infusion, and at 40, 100, and 120 minutes after each infusion, and again at weekly intervals following the third (final) KET infusion for 4 weeks, using standardized rating scales. Those who achieve positive response (>50% decrease in questionnaire total score from baseline) will be given 4 additional once-weekly KET infusions (same dose and infusion rate).
- Conditions
- Treatment Resistant Depression
- Being tested
- Lithium, Placebo, Ketamine
- Keywords
- depression, bipolar I disorder, bipolar II disorder
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Also called Lithane, Lithobid
Lithium will be dosed in units (LI level > or = 0.4 milliequivalents (mEq)/L)
PlaceboDrug
Placebo tablets, dosed in units
KetamineDrug
Also called Ketalar
All subjects will receive 3 IV ketamine infusions of 0.5mg/kg, over 100 min. over 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine plus Lithium | Active comparator | Lithium will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of lithium treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and lithium treatment . Receives: Drug: Lithium; Drug: Ketamine |
| Ketamine plus Placebo | Placebo comparator | Placebo tablets will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of placebo treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and placebo treatment. Receives: Drug: Placebo; Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).
Measured: baseline, at the end of the first infusion (approximately 1 day)
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).
Measured: baseline, at the end of third infusion (approximately 7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2017
- Study start30 Nov 2017
- Primary completionDec 2018 (estimated)
- Study completionDec 2018 (estimated)
Why it stopped: Principal Investigator moved to Jacksonville, FL campus.
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 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- William V. Bobo, M.D.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, William V. Bobo, M.D., Mayo Clinic
- Investigators
- William V Bobo, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03290963
- Sponsor's protocol ID
- 17-000819
- Status last verified
- Aug 2018
- First submitted
- 20 Sep 2017
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting mTOR/GSK3 With Lithium Augmentation to Enhance and Sustain Rapid Antidepressant Actions of Ketamine in Adults With Treatment-Resistant Depression: A Precision Medicine Approach for Psychiatry
- ClinicalTrials.gov ID
- NCT03290963
- Acronym / sponsor ID
- 17-000819
- Conditions
- Treatment Resistant Depression
- Keywords
- depression, bipolar I disorder, bipolar II disorder
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Principal Investigator moved to Jacksonville, FL campus.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- William V. Bobo, M.D.University, hospital or other
- Study start
- 30 Nov 2017 (actual)
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 25 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to compare the antidepressant effect of lithium versus placebo in adults receiving ketamine. Lithium is available commercially for depression; ketamine is available commercially and can help the symptoms of depression; however, it has not been approved by the U.S. Food and Drug Administration (FDA) for this use. The FDA has allowed the use of this drug in this research study.
Detailed description
This is a randomized clinical trial in adults with Treatment-Resistant Depression. All participants will receive three intravenous (IV) Ketamine (KET) infusions over 7 days. Before receiving the first KET infusion, subjects will be randomized to 2 weeks of pre-KET treatment with either Lithium or matching placebo. Pre-treatment medications will then be continued in a double-blind manner during the acute phase administration of ketamine. Questionnaires will be administered at baseline, prior to each KET infusion, and at 40, 100, and 120 minutes after each infusion, and again at weekly intervals following the third (final) KET infusion for 4 weeks, using standardized rating scales. Those who achieve positive response (>50% decrease in questionnaire total score from baseline) will be given 4 additional once-weekly KET infusions (same dose and infusion rate).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine plus Lithium | Active comparator | Drug: Lithium, Drug: KetamineLithium will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of lithium treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and lithium treatment . |
| Ketamine plus Placebo | Placebo comparator | Drug: Placebo, Drug: KetaminePlacebo tablets will be used in conjunction to Ketamine infusions for the treatment of major depression disorder or bipolar disorder type I or II. Before the first ketamine infusion, subjects will be randomized to 2 weeks of placebo treatment. All subjects will receive three IV ketamine infusions (0.5 mg/kg, over 100 min.) over 7 days. Those who achieve positive response (>50% decrease in MADRS total score from baseline) will be given 4 additional once-weekly ketamine infusions (same dose and infusion rate) and placebo treatment. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Ability to provide informed consent;
- Current psychiatric inpatient (voluntary only) or outpatient treatment;
- Meets Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) diagnostic criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder;
- 9-item Patient Health Questionnaire (PHQ-9) total score > 15 at screening and at baseline (just prior to first acute phase ketamine infusion);
- Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode. Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT);
Key exclusion criteria (22 listed)
- Diagnosis of schizophrenia, schizoaffective disorder, or active psychotic symptoms;
- On active lithium treatment;
- Serious risk for suicide, as assessed by the evaluating study clinician; a serious suicide risk will be considered: (a) an inability to control suicide impulses or imminent or unacceptably high risk of suicide in the investigator's judgment; or (b) a recent history of suicidal behavior, which is defined as either one or more suicide attempts (or interrupted suicide attempts) in the 12 months before study entry; or (c) history of serious suicidal behavior, defined as one or more suicide attempts (or interrupted attempts) in the last 3 years with a potential lethality judged by the evaluating study clinician to have possibly resulted in serious injury or death;
- Ongoing prescription of > 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;
- Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression;
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 |
|---|---|---|
| LithiumAlso: Lithane, LithobidLithium will be dosed in units (LI level > or = 0.4 milliequivalents (mEq)/L) | Drug | Ketamine plus Lithium |
| PlaceboPlacebo tablets, dosed in units | Drug | Ketamine plus Placebo |
| KetamineAlso: KetalarAll subjects will receive 3 IV ketamine infusions of 0.5mg/kg, over 100 min. over 7 days. | Drug | Ketamine plus Lithium, Ketamine plus Placebo |
Primary outcome
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: baseline, at the end of the first infusion (approximately 1 day)
The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: baseline, at the end of third infusion (approximately 7 days)
The Montgomery Asberg Depression Scale (MADRS) is a 10-item observer rating scale assessing symptoms of depression. The score ranges from 0 (no depression) to 60 (very depressed).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2018.
- 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.
William V Bobo principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Lithium and Ketamine in people with Treatment Resistant Depression, run by William V. Bobo, M.D. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 22 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: withdrawn, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Change in Montgomery-Asberg Depression Rating Scale (MADRS) (time frame: baseline, at the end of the first infusion (approximately 1 day)). 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?
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 16 Aug 2018.