Trial Outcomes & Findings for Ketamine Treatment Effects on Synaptic Plasticity in Depression (NCT NCT04091971)
NCT ID: NCT04091971
Last Updated: 2023-11-13
Results Overview
PET imaging measure of synaptic density (\[11C\]UCB-J binding potential, BPND) before and after ketamine treatment. This type of brain scan takes pictures to measure the density of synapses, or connections between brain cells (neurons), in the brain. \[11C\]UCB-J is a radiotracer specific for SV2A, a protein present in presynaptic vesicles. \[11C\]UCB-J BPND was quantified in a brain region called the medial prefrontal cortex; previous studies have found lower levels of \[11C\]UCB-J binding in patients with more severe depression. BPND is the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue. Time frame of assessment: Time frame 1 = baseline. This pre-treatment PET scan was acquired as close as possible prior to the first ketamine infusion, up to 7 days prior to first ketamine infusion. Time frame 2 = post-treatment. This post-treatment PET scan was acquired 24-48 hours following the final (4th) ketamine infusion.
COMPLETED
PHASE4
9 participants
Measured at two time frames: Time frame 1 = Baseline. Time frame 2 = post-treatment
2023-11-13
Participant Flow
Participant milestones
| Measure |
Depressed Adults With Current MDD
Subjects will undergo 4 sequential intravenous infusions of ketamine administered over a two week period.
Ketamine is administered at a dose of 0.5mg/kg intravenously as a slow continuous infusion over approximately 40 minutes, with 4 sequential infusions over an approximately two week period (two infusions per week for two weeks).
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
5
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
Depressed Adults With Current MDD
Subjects will undergo 4 sequential intravenous infusions of ketamine administered over a two week period.
Ketamine is administered at a dose of 0.5mg/kg intravenously as a slow continuous infusion over approximately 40 minutes, with 4 sequential infusions over an approximately two week period (two infusions per week for two weeks).
|
|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
|
Overall Study
No longer met eligibility criteria after enrollment.
|
2
|
|
Overall Study
Panic attack during MRI; no MRI or PET but completed ketamine and other procedures
|
1
|
Baseline Characteristics
Ketamine Treatment Effects on Synaptic Plasticity in Depression
Baseline characteristics by cohort
| Measure |
Depressed Adults With Current MDD
n=6 Participants
Subjects will undergo 4 sequential intravenous infusions of ketamine administered over a two week period.
Ketamine: See arm description.
|
|---|---|
|
Age, Continuous
|
37.33 years
STANDARD_DEVIATION 3.83 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
4 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
6 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Measured at two time frames: Time frame 1 = Baseline. Time frame 2 = post-treatmentPopulation: Participants with MDD who completed PET imaging pre-post a course of ketamine infusions for depression
PET imaging measure of synaptic density (\[11C\]UCB-J binding potential, BPND) before and after ketamine treatment. This type of brain scan takes pictures to measure the density of synapses, or connections between brain cells (neurons), in the brain. \[11C\]UCB-J is a radiotracer specific for SV2A, a protein present in presynaptic vesicles. \[11C\]UCB-J BPND was quantified in a brain region called the medial prefrontal cortex; previous studies have found lower levels of \[11C\]UCB-J binding in patients with more severe depression. BPND is the ratio at equilibrium of specifically bound radioligand to that of nondisplaceable radioligand in tissue. Time frame of assessment: Time frame 1 = baseline. This pre-treatment PET scan was acquired as close as possible prior to the first ketamine infusion, up to 7 days prior to first ketamine infusion. Time frame 2 = post-treatment. This post-treatment PET scan was acquired 24-48 hours following the final (4th) ketamine infusion.
Outcome measures
| Measure |
Depressed Adults With Current MDD
n=5 Participants
Subjects will undergo 4 sequential intravenous infusions of ketamine administered over a two week period.
Ketamine: See arm description.
|
|---|---|
|
Synaptic Density
Pre-treatment [11C]UCB-J binding potential (BPnd) in medial prefrontal cortex
|
2.40 Ratio
Standard Deviation 0.81
|
|
Synaptic Density
Post-treatment [11C]UCB-J binding potential (BPnd) in medial prefrontal cortex
|
2.32 Ratio
Standard Deviation 0.67
|
SECONDARY outcome
Timeframe: Measured at 3 time frames. Time frame one = Baseline: 24 hours prior to infusion one ("PRE"). Time frame two = 24 hours following ketamine infusion 4 ("POST1"). Time frame three = one week following ketamine infusion 4 ("POST2").Population: Including all participants with HDRS data, n=6. 1 of the 6 does not have PET data. Including data from the 3 time points relevant for analysis: 24 hours prior to first ketamine infusion ("PRE"), 24 hours following ketamine infusion 4 ("POST1") and 1 week following ketamine infusion 4 ("POST2").
The 17-item Hamilton Depression Rating Scale (HDRS) is a clinician-administered scale that quantifies depression severity, and includes items assessing mood, suicidal thinking, insomnia, feelings of guilt, work and activities, somatic symptoms, and insight. It is a well-characterized scale with excellent psychometric properties. The version of the scale used in this study has a range from 0 to 51. Interpretation of score values is as follows: None: 0-7 Mild: 8-13 Moderate: 14-19 Severe: 20-25 Very Severe: 26-51
Outcome measures
| Measure |
Depressed Adults With Current MDD
n=6 Participants
Subjects will undergo 4 sequential intravenous infusions of ketamine administered over a two week period.
Ketamine: See arm description.
|
|---|---|
|
17-item Hamilton Depression Rating Scale
HAM-17 24 hours prior to first ketamine infusion ("PRE")
|
19.5 score on a scale
Standard Deviation 3.0
|
|
17-item Hamilton Depression Rating Scale
HAM-17 24 hours following ketamine infusion 4 ("POST1")
|
6.5 score on a scale
Standard Deviation 2.4
|
|
17-item Hamilton Depression Rating Scale
HAM-17 1 week following ketamine infusion 4 ("POST2")
|
7.8 score on a scale
Standard Deviation 4.4
|
Adverse Events
Depressed Adults With Current MDD
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Depressed Adults With Current MDD
n=9 participants at risk
Subjects will undergo 4 sequential intravenous infusions of ketamine administered over a two week period.
Ketamine: Ketamine is administered at a dose of 0.5mg/kg intravenously as a slow continuous infusion over approximately 40 minutes, with 4 sequential infusions over an approximately two week period (two infusions per week for two weeks).
|
|---|---|
|
Nervous system disorders
Insomnia
|
22.2%
2/9 • Number of events 2 • 4 weeks
No differences
|
|
Nervous system disorders
Nightmares
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Nervous system disorders
Drowsiness
|
22.2%
2/9 • Number of events 4 • 4 weeks
No differences
|
|
Nervous system disorders
Feeling nervous or hyper
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Nervous system disorders
Irritability
|
22.2%
2/9 • Number of events 2 • 4 weeks
No differences
|
|
Nervous system disorders
Memory difficulties
|
22.2%
2/9 • Number of events 7 • 4 weeks
No differences
|
|
Nervous system disorders
Trouble concentrating
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Nervous system disorders
Headache
|
22.2%
2/9 • Number of events 3 • 4 weeks
No differences
|
|
Ear and labyrinth disorders
Ringing in Ears or Trouble Hearing
|
22.2%
2/9 • Number of events 2 • 4 weeks
No differences
|
|
General disorders
Drooling or Increased Salivation
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Cardiac disorders
Heartbeat rapid or pounding
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Respiratory, thoracic and mediastinal disorders
Trouble catching breath or hyperventilation
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Cardiac disorders
Chest pain
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Gastrointestinal disorders
Nausea or vomiting
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Renal and urinary disorders
Frequent need to urinate
|
22.2%
2/9 • Number of events 4 • 4 weeks
No differences
|
|
Reproductive system and breast disorders
Loss of Sexual Interest
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Reproductive system and breast disorders
Delayed or absent orgasm
|
11.1%
1/9 • Number of events 5 • 4 weeks
No differences
|
|
General disorders
Excessive Sweating
|
33.3%
3/9 • Number of events 6 • 4 weeks
No differences
|
|
Gastrointestinal disorders
Decreased appetite
|
33.3%
3/9 • Number of events 4 • 4 weeks
No differences
|
|
Gastrointestinal disorders
Increased appetite
|
11.1%
1/9 • Number of events 4 • 4 weeks
No differences
|
|
General disorders
Weight loss
|
11.1%
1/9 • Number of events 2 • 4 weeks
No differences
|
|
Skin and subcutaneous tissue disorders
Skin rash or allergy
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Nervous system disorders
Word finding difficulties
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
Nervous system disorders
Apathy/emotional indifference
|
11.1%
1/9 • Number of events 1 • 4 weeks
No differences
|
|
General disorders
Hair thinning/loss
|
22.2%
2/9 • Number of events 2 • 4 weeks
No differences
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place