Healthy ControlsPhase 4NCT02134951
Biomarker Assessment of Glutamatergic Target Engagement
A Phase 4 study testing Ketamine and Normal saline in people with Healthy Controls, run by New York State Psychiatric Institute at 3 sites in United States.
Trial summary
The purpose of this study is to assess the relative feasibility of 2 potential functional measures of target engagement (Glx MRS, BOLD fMRI) to systematically assess mGluR 2/3 in drug development for psychotic spectrum disorders. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Controls
- What is being tested?
- Ketamine and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 65 participants
- Where
- 3 sitesUnited States
- Study dates
- May 2014to Nov 2015
- Phase
- Phase 4
- 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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 18-55
- Negative Urine Toxicology
- No present or past psychiatric conditions (including substance abuse or dependence, with the exception of nicotine dependence)
- No family history of schizophrenia in a first-degree relative
Who cannot join
- Any current DSM IV Axis I disorder and/or past substance abuse of dependence (nicotine dependence is allowed)
- Any current use of amphetamines, opiates, cocaine, sedative-hypnotics, or cannabis
- Current (i.e., within the last 3 months) treatment with any psychotropic medications
- Pregnancy, lactation, or lack of use of effective birth control
- Presence of positive history of significant medical or neurological illness (including any history of seizure), including high blood pressure (SBP >140, DBP >90), low blood pressure (SBP <100, DBP <60), orthostatic BP change>20% (1/3 SBP + 2/3 DBP) or cardiac illness or resting heart rate >100 or <50
- History of significant violent behavior
Show all 9Show fewer
- History of recreational ketamine use, recreational PCP use, or an adverse reaction to ketamine. Subjects who have participated prior research ketamine studies will be eligible providing they have participated in no more than 5 previous research ketamine infusions. Subjects can have infusions not more frequently than biweekly and not more than 1/month on average, therefore subjects entering the study will need to wait 1 month if they had a single infusion and 6 weeks if they have had two closely spaced infusions.
- Contraindication to MRI scanning, including metal implants or claustrophobia. Metal implants, pacemaker, other metal (e.g. shrapnel or surgical prostheses) or paramagnetic objects contained within the body which may present a risk to the subject or interfere with the MR scan, as determined in consultation with a neuroradiologist and according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects", F.G. Shellock, Lippincott Williams and Wilkins NY 2001
- Color Blindness
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Yale University
New Haven, Connecticut, 06511
New York State Psychiatric Institute
New York, New York, 10032
University of California Davis
Sacramento, California, 95817
About this study
The purpose of this study is to assess the relative feasibility of 2 potential functional measures of target engagement (Glx MRS, BOLD fMRI) to systematically assess mGluR 2/3 in drug development for psychotic spectrum disorders.
Read the detailed description
This is a pilot study of healthy subject to assess the feasibility of Glx MRS and BOLD fMRI to measure ketamine induced changes in glutamatergic indices. The investigators will randomize 18 subjects at each site. Subjects will be randomized to ketamine or placebo in a 2:1 ratio and receive two drug challenges separated by at least two weeks. Ketamine challenge is used to induce a "glutamate surge" within prefrontal brain regions that can be detected using neurochemical and functional imaging techniques. Each subject will receive MRS and BOLD fMRI during each challenge day. The goal of the pilot study is to assess the feasibility of both the proposed ketamine challenge paradigm and of the proposed imaging-based biomarkers. Specific indices to be used in assessing feasibility will include effect size, cross-site and cross-subject reliability, safety, and subject tolerability as similar studies will be performed independently at Yale and UC Davis. Second this information will be used to select and refine final study parameters for a subsequent full proof-of-clinical mechanism (POCM) study investigating the effect of Pomaglumetad on ketamine-induced MRS and fMRI effects.
- Conditions
- Healthy Controls
- Being tested
- Ketamine, Normal saline
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called ketamine hydrochloride
intravenous infusion of saline solution with ketamine
Normal salineDrug
Also called saline
Normal saline will be used for placebo in this group
| Study group | Role | What they receive |
|---|---|---|
| ketamine | Experimental | IV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes Receives: Drug: Ketamine |
| Placebo | Placebo comparator | Placebo group will receive normal saline Receives: Drug: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glutamate + Glutamine (Glx) Response
Compare changes in Glx response to infusion of ketamine vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the Glx over creatinine ratios, with higher values indicating higher Glx/creatinine ratios.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2014 (estimated)
- Study startMay 2014
- Primary completionOct 2015
- Study completionNov 2015
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 Healthy ControlsStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Marlene Carlson, New York State Psychiatric Institute
- Investigators
- Jeffrey A Lieberman, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02134951
- Sponsor's protocol ID
- 6925
- Other IDs
- HHS-N-271-2012-0000-7-I
- Status last verified
- Aug 2018
- First submitted
- 7 May 2014
- Last updated
- 17 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Jan 1;75(1):11-19. doi: 10.1001/jamapsychiatry.2017.3572.
PubMed 29167877
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarker Assessment of Glutamatergic Target Engagement
- ClinicalTrials.gov ID
- NCT02134951
- Acronym / sponsor ID
- 6925
- Conditions
- Healthy Controls
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- May 2014
- Primary completion
- Oct 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 9 May 2014 (estimated)
- Results
- Posted 13 Feb 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 assess the relative feasibility of 2 potential functional measures of target engagement (Glx MRS, BOLD fMRI) to systematically assess mGluR 2/3 in drug development for psychotic spectrum disorders.
Detailed description
This is a pilot study of healthy subject to assess the feasibility of Glx MRS and BOLD fMRI to measure ketamine induced changes in glutamatergic indices. The investigators will randomize 18 subjects at each site. Subjects will be randomized to ketamine or placebo in a 2:1 ratio and receive two drug challenges separated by at least two weeks. Ketamine challenge is used to induce a "glutamate surge" within prefrontal brain regions that can be detected using neurochemical and functional imaging techniques. Each subject will receive MRS and BOLD fMRI during each challenge day. The goal of the pilot study is to assess the feasibility of both the proposed ketamine challenge paradigm and of the proposed imaging-based biomarkers. Specific indices to be used in assessing feasibility will include effect size, cross-site and cross-subject reliability, safety, and subject tolerability as similar studies will be performed independently at Yale and UC Davis. Second this information will be used to select and refine final study parameters for a subsequent full proof-of-clinical mechanism (POCM) study investigating the effect of Pomaglumetad on ketamine-induced MRS and fMRI effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ketamine | Experimental | Drug: KetamineIV infusion of ketamine 0.23mg/kg bolus over 1 minutes followed by 0.58 mg/kg/hr over 30 minutes then 0.29mg/kg/hr over 64 minutes |
| Placebo | Placebo comparator | Drug: Normal salinePlacebo group will receive normal saline |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age 18-55
- Negative Urine Toxicology
- No present or past psychiatric conditions (including substance abuse or dependence, with the exception of nicotine dependence)
- No family history of schizophrenia in a first-degree relative
Key exclusion criteria (9 listed)
- Any current DSM IV Axis I disorder and/or past substance abuse of dependence (nicotine dependence is allowed)
- Any current use of amphetamines, opiates, cocaine, sedative-hypnotics, or cannabis
- Current (i.e., within the last 3 months) treatment with any psychotropic medications
- Pregnancy, lactation, or lack of use of effective birth control
- Presence of positive history of significant medical or neurological illness (including any history of seizure), including high blood pressure (SBP >140, DBP >90), low blood pressure (SBP <100, DBP <60), orthostatic BP change>20% (1/3 SBP + 2/3 DBP) or cardiac illness or resting heart rate >100 or <50
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 |
|---|---|---|
| KetamineAlso: ketamine hydrochlorideintravenous infusion of saline solution with ketamine | Drug | ketamine |
| Normal salineAlso: salineNormal saline will be used for placebo in this group | Drug | Placebo |
Primary outcome
Glutamate + Glutamine (Glx) Response
Time frame: Day 1
Compare changes in Glx response to infusion of ketamine vs placebo, as measured by proton magnetic resonance spectroscopy (¹H MRS). Calculated by post-pre changes in the Glx over creatinine ratios, with higher values indicating higher Glx/creatinine ratios.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29167877Javitt DC, Carter CS, Krystal JH, Kantrowitz JT, Girgis RR, Kegeles LS, Ragland JD, Maddock RJ, Lesh TA, Tanase C, Corlett PR, Rothman DL, Mason G, Qiu M, Robinson J, Potter WZ, Carlson M, Wall MM, Choo TH, Grinband J, Lieberman JA. Utility of Imaging-Based Biomarkers for Glutamate-Targeted Drug Development in Psychotic Disorders: A Randomized Clinical Trial. JAMA Psychiatry. 2018 Jan 1;75(1):11-19. doi: 10.1001/jamapsychiatry.2017.3572.
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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.
Jeffrey A Lieberman, MD principal investigator
New York State Psychiatric Institute
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine and Normal saline in people with Healthy Controls, run by New York State Psychiatric Institute at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 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 17 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 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 13 Feb 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?
Glutamate + Glutamine (Glx) Response (time frame: Day 1). 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 NCT02134951, 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 17 Aug 2018.