Major Depressive DisorderNCT01691092

PET Imaging of mGLuR5 With Drug Challenge

A study testing Ketamine in people with Major Depressive Disorder and Post-Traumatic Stress Disorder (PTSD), run by Yale University at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is designed to look at that involvement of a process in the brain called the glutamate system in depression. Participants will undergo a screening session, up to two functional Magnetic Resonance Imaging (fMRI) scans, and up to three Positron Emission Tomography (PET) scans, as well as cognitive testing at… Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Major Depressive Disorder, Post-Traumatic Stress Disorder (PTSD)
What is being tested?: Ketamine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 79 participants
Where: 3 sitesUnited States
Study dates: Jun 2012to Feb 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 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

18-65 years old
English speaking
No other Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnosis present, besides required as below.
clinical diagnosis of a current or past depressive episode
medication free for at least 2 weeks
Score >16 on Hamilton Depression Rating Scale (HDRS) if currently depressed or <11 if not currently depressed

Show all 12Show fewer

treatment or non-treatment seeking who understand that this study is for research purposes only
no current, or history of, any DSM-IV diagnosis
no first-degree relative with history of psychotic, mood, or anxiety disorder
current Post-Traumatic Stress Disorder, as determined by the Structured Clinical Interview for DSM-IV-Text Revision (TR) (SCID) patient research edition
Clinician Administered PTSD Scale for DSM-IV-TR (CAPS) score of 50 or higher
-history of trauma (meeting the criterion A of PTSD but not a full diagnosis of PTSD)

Who cannot join

Current or past significant medical, neurological, or metabolic disorder or loss of consciousness for 5 minutes or more
active, significant suicidal ideation
implanted metallic devices or any Magnetic Resonance (MR) contraindications
women who are pregnant or breastfeeding
met DSM-IV criteria for alcohol/illicit substance dependence in their life-time or met alcohol/illicit substance abuse within past year
history of prior radiation exposure for research purposes within the past year such that participation in this study would place them over FDA limits for annual radiation exposure. This guideline is an effective dose of 5 rem received per year

Show all 9Show fewer

blood donation within eight weeks of the start of the study
radiation exposure at work that precludes study participation
blood pressure >140/80

Trial locations and contacts

3 sites in 1 country.

United States3 sites

Connecticut Mental Health Center
New Haven, Connecticut, 06519
Yale University Magnetic Resonance Research Center (MRRC)
New Haven, Connecticut, 06519
Yale University PET Center
New Haven, Connecticut, 06519

Other trials in United States

About this study

Official title: PET Imaging of mGluR5 With Drug Challenge

Hypothesis 1: The investigators hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5.

Hypothesis 2: The investigators hypothesize an improvement in memory and attentional skills after drug challenge.

Hypothesis 3: The investigators hypothesize an increase in mGluR5 availability and change in MRI measures post drug challenge as compared to baseline, signifying synaptogenesis.

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.

Read the detailed description

Aim 1: To determine the acute effect of medication-induced glutamate release on mGluR5 availability in human subjects. Hypothesis 1: We hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5 availability.

Aim 2: To determine if glutamate release via administration of ketamine or NAC has pro cognitive benefits.

Hypothesis 2: We hypothesize an improvement in memory and attentional skills after drug challenge.

Aim 3: To determine if there is synaptogenesis detectable by PET and MRI post ketamine or NAC within a week of drug challenge (at the time of greatest antidepressant response). Hypothesis 3: We hypothesize an increase in mGluR5 availability and change in MRI measures, post drug challenge as compared to baseline, signifying synaptogenesis.

Aim 4: To determine if there is a difference in reduction of mGluR5 availability after ketamine administration when radiotracer is administered bolus as compared to bolus to constant infusion in the same subjects (ABP688 radiotracer only).

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.

Conditions: Major Depressive Disorder, Post-Traumatic Stress Disorder (PTSD)
Being tested: Ketamine
Keywords: Depression, Ketamine, PET, PTSD
Medical subject headings: Depressive Disorder, Major, Stress Disorders, Post-Traumatic, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

KetamineDrug
Also called ketamine IV
All subjects will receive ketamine to induce glutamate release in the brain

Study groups in NCT01691092
Study group	Role	What they receive
Ketamine	Experimental	All subjects will receive ketamine Receives: Drug: Ketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging
PET imaging obtained in healthy and Major Depressive Disorder (MDD) subjects. Glutamate levels determined by radiotracer uptake in PET images.
Measured: 1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan; scan 3: 90 minute scan 24 hours post ketamine

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 2012Feb 2016

First posted24 Sep 2012 (estimated)
Study startJun 2012
Primary completionFeb 2016
Study completionFeb 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.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by Yale UniversityThe 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: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 79 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01691092
Sponsor's protocol ID: 1111009365
Status last verified: Mar 2017
First submitted: 19 Sep 2012
Last updated: 21 Apr 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: PET Imaging of mGluR5 With Drug Challenge
ClinicalTrials.gov ID: NCT01691092
Acronym / sponsor ID: 1111009365
Conditions: Major Depressive Disorder, Post-Traumatic Stress Disorder (PTSD)
Keywords: Depression, Ketamine, PET, PTSD
Study type: Interventional
Recruitment status: Completed
Enrolment: 79 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Study start: Jun 2012
Primary completion: Feb 2016 (actual)
Study completion: Feb 2016 (actual)
First posted: 24 Sep 2012 (estimated)
Results: Posted 21 Apr 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Hypothesis 1: The investigators hypothesize administration of ketamine or n-acetylcysteine (NAC) will lead to a decrease in mGluR5.

Hypothesis 2: The investigators hypothesize an improvement in memory and attentional skills after drug challenge.

Hypothesis 3: The investigators hypothesize an increase in mGluR5 availability and change in MRI measures post drug challenge as compared to baseline, signifying synaptogenesis.

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.

Detailed description

Aim 2: To determine if glutamate release via administration of ketamine or NAC has pro cognitive benefits.

Hypothesis 2: We hypothesize an improvement in memory and attentional skills after drug challenge.

Hypothesis 4: We expect there should not be a significant difference in reduction in mGluR5 availability due to differences in ABP688 radiotracer infusion.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Ketamine	Experimental	Drug: KetamineAll subjects will receive ketamine

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

18-65 years old
English speaking
No other Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) diagnosis present, besides required as below.
clinical diagnosis of a current or past depressive episode
medication free for at least 2 weeks

Key exclusion criteria (9 listed)

Current or past significant medical, neurological, or metabolic disorder or loss of consciousness for 5 minutes or more
active, significant suicidal ideation
implanted metallic devices or any Magnetic Resonance (MR) contraindications
women who are pregnant or breastfeeding
met DSM-IV criteria for alcohol/illicit substance dependence in their life-time or met alcohol/illicit substance abuse within past year

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 IVAll subjects will receive ketamine to induce glutamate release in the brain	Drug	Ketamine

Primary outcome

Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging
Time frame: 1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan; scan 3: 90 minute scan 24 hours post ketamine
PET imaging obtained in healthy and Major Depressive Disorder (MDD) subjects. Glutamate levels determined by radiotracer uptake in PET images.

Results and safety

Results posted to the registry on 21 Apr 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Ketamine	79	38

Primary outcome: Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging

Time frame: 1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan; scan 3: 90 minute scan 24 hours post ketamine. Mean (Standard Deviation). Unit: percentage reduction

Measure	Ketamine n = 27
HC % reduction from baseline immediately post ket	19 (22)
MDD % reduction from baseline immediately post ket	14 (9)
HC % reduction from baseline 24 hrs post ket	31 (30)
MDD % reduction from baseline 24 hrs post ket	14 (13)

Population analysed: 13 healthy (6 males, 7 females) and 14 MDD non-smokers (4 males, 10 females) Mean age: 33.5 ± 13.2 yrs reasons for discrepancy (participant flow module): some data was not able to be analyzed due to elevated metabolites; some subject did not tolerate ketamine and had to be pulled out of scanner so we could not obtain data.

Adverse events

Time frame: 4 years. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Ketamine	1 of 38 (2.6%)	0 of 38 (0%)	Not reported

Limitations and caveats (from the sponsor): Study lacks placebo control group Hemodynamic effects of ketamine may alter tracer delivery and washout Study lacks long-term follow up Only non-smokers studied Ketamine dose administered is higher than typical dose used for clinical purposes

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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.

Irina Esterlis, PhD principal investigator

Yale University

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Ketamine in people with Major Depressive Disorder and Post-Traumatic Stress Disorder (PTSD), run by Yale University 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 12 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 21 Apr 2017. 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. 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 21 Apr 2017). 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?

Change in Glutamate Levels at Baseline and After Ketamine Administration as Confirmed by Positron Emission Tomography (PET) Imaging (time frame: 1st scan: 90 minute baseline scan; 2nd scan: 90 minutes, ketamine administration at start of scan; scan 3: 90 minute scan 24 hours post ketamine). 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 NCT01691092.

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 21 Apr 2017.