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RecruitingEarly Phase 1

Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine

Establishing Glutamatergic Changes as the Mechanism of Action in the Rapid Antidepressant Effects of Ketamine

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
25 Years to 65 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

  • Procedures mentioned: Interviews, Infusions, MRI scans

Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.

Show the study's own words
  • "Medical history), Structured Clinical Interview for DSMV (SCID) and clinician-administered measures of mood to determine final study eligibility."
  • "In-laboratory Ketamine Infusion Protocol: On the study day, participants will arrive at the Hospital of the University of Pennsylvania at 9:00 AM."
  • "After initial orientation, they will undergo a baseline MRI scan between 9:00 AM and 11:00 AM."
  • "The MRI will utilize a 7T Siemens Terra system for high-resolution GluCEST imaging to capture glutamatergic activity."
  • "A light snack will be provided before the ketamine infusion begins between 12:00 PM and 1:00 PM."
  • "Participants will receive a 40-minute infusion of ketamine (0.5 mg/kg) under the supervision of a registered nurse and anesthesiologist."
Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study looks at how ketamine may quickly improve mood by changing glutamate, a brain chemical that helps brain cells communicate. It is for 10 adults ages 25–65 with major depression that has not improved with treatment. Participants will have brain scans and mood checks before and after getting ketamine through a vein.

In the treatment of Major Depressive Disorder (MDD), ketamine can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as ketamine has been suggested to increase synaptic strength. Although determining how ketamine impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of ketamine. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity to assess synaptic strength following ketamine administration. Ten individuals (aged 25-65) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following ketamine infusion. Both clinician-administered and subjective mood measures will be collected. It is predicted that ketamine will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You are 25–65 years old.
  • A study interview confirms that you currently have depression.
  • At least two antidepressant or mood-stabilizing treatments have failed during your current period of depression. Drug treatments must have been tried at an adequate dose for at least 8 weeks.
  • You can understand English, which is used for all study forms.
  • You can agree to take part and pass a test about ketamine’s effects and the study’s goals and rules.

Who can't join

  • You have a sleep disorder other than insomnia (trouble sleeping), currently smoke, or have abused alcohol or drugs in the past year.
  • You have a history of bipolar disorder, severe confusion, dementia, a memory disorder, schizophrenia, or other disorders that affect your sense of reality. Developmental delays or intellectual disabilities also rule out joining.
  • You have a major illness affecting brain function or your ability to take part; a past head injury with major loss of consciousness; or severe confusion or brain dysfunction diagnosed or reported within the past 12 months.
  • You have metal implants, a pacemaker, tattoos, or another reason you cannot have an MRI scan. You cannot tolerate the scanner or feel very afraid in closed spaces.
  • You are pregnant, have untreated high blood pressure, or have a BMI over 40. BMI is a measure based on height and weight.
  • You take naltrexone; take a daily benzodiazepine dose equal to 4 mg of lorazepam; or take any benzodiazepine in the morning when you are assessed. Benzodiazepines are medicines often used for anxiety or sleep.
  • You use an MAOI antidepressant within 2 weeks before ketamine, or carbamazepine or modafinil within 2 weeks before or at least 24 hours after the last ketamine dose.
  • You currently get electrical, magnetic, or nerve-stimulation treatment for depression, including ECT, TMS, vagal nerve stimulation, or deep brain stimulation. You have previously joined a ketamine study for depression or used ketamine for treatment or recreation.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion Criteria: 1. Age between 25 and 65 years; 2. Current depression as assessed on the SCID; 3. 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 4. Able to comprehend English, as all questionnaires are in this language 5. Ability to provide informed consent Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria. Exclusion Criteria: 1. A sleep disorder other than insomnia, as determined by history; 2. History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID; 3. Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen; 4. A current smoker; 4\) Any significant medical or neurological illness that impacts brain function or impedes participation; 5) History of head trauma with significant loss of consciousness; 6) Metallic implants, pacemakers or tattoos, or other contraindications to MRI; Claustrophobic, or intolerant of the scanner environment; 7) For women, pregnancy will exclude participation. 8) Untreated hypertension Based on ketamine's known difficulties with induction of perceptual/psychomimetic symptoms, exclusion criteria for this study are as follows: 1. Patients with a BMI over 40. 2. Ongoing prescription of 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment; 3. Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression; 4. Use of any MAOI is prohibited two weeks prior to administration of study drug; if patients are on an MAOI when enrolled, study drug will not be administered until two weeks off MAOI; 5. CYP3A4 inducers carbamazepine and modafinil are prohibited two weeks prior to administration of study drug and at least 24 hours after last dose of study drug. 6. Current use of Naltrexone; 7. Developmental delay, mental retardation, or intellectual disorder; 8. Clinical or self-reported diagnosis of delirium, encephalopathy, or related clinical diagnosis within the prior 12 months; 9. Prior participation in another study of ketamine for depression 10. Prior treatment and/or recreational use of ketamine

Study sites (1)

PA