DepressionPhase 2NCT01880593
Ketamine Plus Lithium in Treatment-Resistant Depression
A Phase 2 study testing Lithium and Ketamine in people with Depression, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
The purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Depression
- What is being tested?
- Lithium and Ketamine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2013to Nov 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients, 21-65 years of age;
- Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum B-HCG at screening and at pre-infusion;
- Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
- Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
- Participants have not responded to two or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
- Current Major Depressive Episode of at least moderate severity, defined as a QIDS-SR score ≥ 14 and a CGI-S score of ≥ 4;Current major depressive episode is of at least 4 weeks duration;
- Each participant must have a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document;
- Each participant must be able to identify a family member, physician, or friend who will participate in the Treatment Contract.
Who cannot join
- Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder;
- Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
- Current diagnosis of OCD or eating disorder (bulimia nervosa or anorexia nervosa);
- Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
- Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
- Patients judged clinically to be at serious and imminent suicidal or homicidal risk;
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- Women who are either pregnant or nursing;
- Serious, unstable medical illnesses including hepatic, renal impairment, gastroenterologic (including gastro-esophageal reflux disease), respiratory (including obstructive sleep apnea, or history of difficulty with airway management during previous anesthetics), cardiovascular (including ischemic heart disease and uncontrolled hypertension), endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
- Clinically significant abnormal findings of laboratory parameters, physical examination, or ECG;
- Patients who have a positive urine toxicology for illicit substances at screening and within 24 hours of the infusion;
- Patients with one or more seizures without a clear and resolved etiology;
- Treatment with an irreversible MAOI within 2 weeks prior to randomization or fluoxetine within 4 weeks prior to randomization;
- Treatment with other antidepressants within one week of randomization;
- Previous recreational use of PCP or ketamine;
- Hypertension (systolic BP >160 mm Hg or diastolic BP >90 mm Hg) not controlled by diuretic or beta-blocker therapy alone or in combination;
- A blood pressure reading over 160/90 or two separate readings over 140/90 at screening or baseline visits;
- Renal impairment, as reflected by a BUN > 20 mg/dL and/or creatinin clearance of >1.3 mg/dL;
- Thyroid impairment, as reflected by a TSH > 4.2 mU/L;
- Cardiac disease, as reflected by an EKG that is abnormal and of concern for cardiac disease;
- Any anticipated change in medications that could affect fluid or salt balance, including the following antihypertensive agents: ACE inhibitor, loop diuretics, calcium channel blockers, thiazide diuretics, angiotensin II receptor blockers.
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: Ketamine Plus Lithium as a Novel Pharmacotherapeutic Strategy in Treatment-Resistant Depression
The purpose of this study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic (a drug used to produce loss of consciousness before and during surgery). Ketamine is not approved for the treatment of major depressive disorder and is considered experimental in this study. An additional purpose of this study is to research the effects of ketamine on brain function.
You may qualify to take part in this research study because you have been diagnosed with major depressive disorder (MDD) and have not responded to past treatments.
Read the detailed description
Major Depressive Disorder (MDD) is a disabling medical illness and current monoaminergic treatments are slow to act and possess only limited efficacy. In this context, the discovery that the glutamate NMDA receptor antagonist ketamine is rapidly antidepressant (onset of action within hours) -- even in patients suffering from treatment-resistant depression (TRD) -- has ignited tremendous enthusiasm among clinicians, scientists and patients alike. A critical obstacle to the translation of this discovery into a novel treatment, however, is the limited duration of action following a course of ketamine (e.g. 1-2 weeks). The current project will address this important gap in medical knowledge by testing a rational neuropharmacological strategy designed to optimize and sustain the rapid antidepressant effects of ketamine. Driven by the recent characterization of the molecular mechanisms underpinning the antidepressant and neuroplasticity effects of ketamine, we will test the combination of ketamine plus lithium in patients with TRD using a randomized, double blind, placebo-controlled design. The primary aims of the project are (1) to test the efficacy of lithium-plus-ketamine compared to placebo-plus-ketamine as an antidepressant combination strategy in TRD and (2) to gather data on the safety and tolerability of the lithium-plus-ketamine.
- Conditions
- Depression
- Being tested
- Lithium, Ketamine, Placebo
- Keywords
- Ketamine, glutamate, N-methyl-D-aspartate, depression, major depressive disorder, treatment resistant, antidepressant, lithium
- Medical subject headings
- Depression, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LithiumDrug
Also called Lithium Carbonate Immediate Release
Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study.
KetamineDrug
PlaceboDrug
Subjects in this arm take placebo pills at night for duration of the study.
| Study group | Role | What they receive |
|---|---|---|
| Ketamine and Lithium | Experimental | Subjects in this arm take 600-1200mg of Lithium pills at night for duration of the study Receives: Drug: Lithium; Drug: Ketamine |
| Ketamine and Placebo | Placebo comparator | Subjects in this arm take placebo pills at night for duration of the study. Receives: Drug: Ketamine; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
MADRS-S Score
The Montgomery Asberg Depression Rating Scale (MADRS-S) has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
Measured: 2 weeks after last ketamine infusion
Secondary outcomes (6)
QIDS-SR Score
Quick Inventory of Depressive Symptomatology, Self-Report (QIDS-SR) score - Each item is rated 0 (no depression) to 3 (severe depression), for a total score range of 0 (no depression) to 27 (severe depression).
Measured: 2 weeks after last ketamine infusion
CGI-S Score
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill.
Measured: 2 weeks after last ketamine infusion
HAM-A Score
Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Measured: 2 weeks after last ketamine infusion
BSS Score
BECK Scale for Suicidal Ideation (BSS) - 0-13 Minimal; 14-19 Mild; 20-28 Moderate; 29-63 Severe
Measured: 2 weeks after last ketamine infusion
CSSRS Score
Columbia Suicide Severity Rating Scale (CSSRS) - Full range from 0 (low intensity suicidal ideation to 9 (high intensity suicidal ideation).
Measured: 2 weeks after last ketamine infusion
Patient Rated Inventory of Side Effects (PRISE)
Number of Participants with PRISE
Measured: 2 weeks after last ketamine infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jun 2013 (estimated)
- Study startJul 2013
- Primary completionNov 2016
- Study completionNov 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 (1)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, James Murrough, Icahn School of Medicine at Mount Sinai
- Investigators
- James W Murrough, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01880593
- Sponsor's protocol ID
- GCO 13-0365
- Status last verified
- Jul 2018
- First submitted
- 14 Jun 2013
- Last updated
- 31 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27.
PubMed 22840761
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine Plus Lithium as a Novel Pharmacotherapeutic Strategy in Treatment-Resistant Depression
- ClinicalTrials.gov ID
- NCT01880593
- Acronym / sponsor ID
- GCO 13-0365
- Conditions
- Depression
- Keywords
- Ketamine, glutamate, N-methyl-D-aspartate, depression, major depressive disorder, treatment resistant, antidepressant, lithium
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- Jul 2013
- Primary completion
- Nov 2016 (actual)
- Study completion
- Nov 2016 (actual)
- First posted
- 19 Jun 2013 (estimated)
- Results
- Posted 31 Jul 2018
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 study is to test the antidepressant effect of ketamine when given repeatedly over a period of 1 week, as well as the use of Lithium as a relapse-prevention strategy for patients with treatment-resistant depression (TRD) who respond to an initial series of ketamine infusions. Ketamine is a Food and Drug Administration approved anesthetic (a drug used to produce loss of consciousness before and during surgery). Ketamine is not approved for the treatment of major depressive disorder and is considered experimental in this study. An additional purpose of this study is to research the effects of ketamine on brain function.
You may qualify to take part in this research study because you have been diagnosed with major depressive disorder (MDD) and have not responded to past treatments.
Detailed description
Major Depressive Disorder (MDD) is a disabling medical illness and current monoaminergic treatments are slow to act and possess only limited efficacy. In this context, the discovery that the glutamate NMDA receptor antagonist ketamine is rapidly antidepressant (onset of action within hours) -- even in patients suffering from treatment-resistant depression (TRD) -- has ignited tremendous enthusiasm among clinicians, scientists and patients alike. A critical obstacle to the translation of this discovery into a novel treatment, however, is the limited duration of action following a course of ketamine (e.g. 1-2 weeks). The current project will address this important gap in medical knowledge by testing a rational neuropharmacological strategy designed to optimize and sustain the rapid antidepressant effects of ketamine. Driven by the recent characterization of the molecular mechanisms underpinning the antidepressant and neuroplasticity effects of ketamine, we will test the combination of ketamine plus lithium in patients with TRD using a randomized, double blind, placebo-controlled design. The primary aims of the project are (1) to test the efficacy of lithium-plus-ketamine compared to placebo-plus-ketamine as an antidepressant combination strategy in TRD and (2) to gather data on the safety and tolerability of the lithium-plus-ketamine.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine and Lithium | Experimental | Drug: Lithium, Drug: KetamineSubjects in this arm take 600-1200mg of Lithium pills at night for duration of the study |
| Ketamine and Placebo | Placebo comparator | Drug: Ketamine, Drug: PlaceboSubjects in this arm take placebo pills at night for duration of the study. |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Male or female patients, 21-65 years of age;
- Female individuals who are not of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year) or using a medically accepted reliable means of contraception. Women using oral contraceptive medication for birth control must also be using a barrier contraceptive. Women of childbearing potential must also have a negative serum B-HCG at screening and at pre-infusion;
- Participants must fulfill DSM-IV criteria for Major Depression without psychotic features, based on clinical assessment by a study psychiatrist and confirmed by a structured diagnostic interview, the Structured Clinical Interview for DSM-IV TR Axis I Disorders, Patient Edition (SCID-P);
- Participants must have a history of at least one previous episode of depression prior to the current episode (recurrent MDD) or have chronic MDD (of at least two years' duration);
- Participants have not responded to two or more adequate trials of an antidepressant as determined by Antidepressant Treatment History Form (ATHF) criteria (score >=3);
Key exclusion criteria (20 listed)
- Lifetime history of psychotic features, diagnosis of schizophrenia or any other psychotic disorder, or diagnosis of bipolar disorder;
- Lifetime histories of autism, mental retardation, pervasive developmental disorders, or Tourette's syndrome;
- Current diagnosis of OCD or eating disorder (bulimia nervosa or anorexia nervosa);
- Subjects with DSM-IV drug or alcohol abuse/dependence within the preceding 2 years;
- Patients with schizotypal or antisocial personality disorder, or any clinically significant axis II disorder that would, in the investigator's judgment, preclude safe study participation;
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: Lithium Carbonate Immediate ReleaseSubjects in this arm take 600-1200mg of Lithium pills at night for duration of the study. | Drug | Ketamine and Lithium |
| Ketamine | Drug | Ketamine and Lithium, Ketamine and Placebo |
| PlaceboSubjects in this arm take placebo pills at night for duration of the study. | Drug | Ketamine and Placebo |
Primary outcome
MADRS-S Score
Time frame: 2 weeks after last ketamine infusion
The Montgomery Asberg Depression Rating Scale (MADRS-S) has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression).
6 secondary outcomes
QIDS-SR Score
Time frame: 2 weeks after last ketamine infusion
CGI-S Score
Time frame: 2 weeks after last ketamine infusion
HAM-A Score
Time frame: 2 weeks after last ketamine infusion
BSS Score
Time frame: 2 weeks after last ketamine infusion
CSSRS Score
Time frame: 2 weeks after last ketamine infusion
Patient Rated Inventory of Side Effects (PRISE)
Time frame: 2 weeks after last ketamine infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 22840761Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, aan het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV. Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry. 2013 Aug 15;74(4):250-6. doi: 10.1016/j.biopsych.2012.06.022. Epub 2012 Jul 27.
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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.
James W Murrough, MD principal investigator
Icahn School of Medicine at Mount Sinai
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 Depression, run by Icahn School of Medicine at Mount Sinai 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 8 inclusion and 20 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 31 Jul 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?
Yes. Results are posted in the registry (first posted 31 Jul 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?
MADRS-S Score (time frame: 2 weeks after last ketamine infusion). 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 NCT01880593, 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 31 Jul 2018.