Depression, Unipolar
Conditions
Brief summary
In this project, we will A) track the functioning of a collection of potential neurobiological targets for depression over time, B) examine how fluctuations in the functioning of those targets relates to real-world functioning, and C) in a subset of the sample, determine how the functioning in those targets is altered by a single dose of ketamine.
Interventions
Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min)
Sponsors
Rebecca Price
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
All participants will: 1. be between the ages of 18 and 60 years, 2. score ≥ 14 on the Hamilton Depression Rating Scale (Ham-D) 3. possess a level of understanding sufficient to agree to all tests and examinations required by the protocol and must sign an informed consent document
Exclusion criteria
All participants: 1. Presence of lifetime bipolar, psychotic, or autism spectrum; current problematic substance use (e.g., ongoing moderate-to-severe substance use disorder); 2. Failure to meet standard MRI inclusion criteria: those who have cardiac pacemakers, neural pacemakers, cochlear implants, metal braces, or other non-MRI-compatible metal objects in their body. History of significant injury or surgery to the brain or spinal cord that would impair interpretation of results. 3. Acute suicidality or other psychiatric crises requiring treatment escalation. We will use the Columbia Suicide Severity Rating Scale (CSSRS) as both an initial
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| fMRI Intrinsic Connectivity: Frontoparietal Control Network | 24hrs post-intervention | functional connectivity normalized correlation values within frontoparietal control network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
| fMRI Intrinsic Connectivity: Default Mode Network | 24hrs post-intervention | functional connectivity normalized correlation values within default mode network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
| fMRI Intrinsic Connectivity: Salience Network | 24hrs post-intervention | functional connectivity normalized correlation values within salience ventral attentional network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
| fMRI Intrinsic Connectivity: Limbic Network | 24hrs post-intervention | functional connectivity normalized correlation values within limbic network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hamilton Depression Rating Scale (Modified Score) | 24hrs post-intervention | Clinician-rated depression (range: 0-52; higher scores = worse outcome) |
| Quick Inventory of Depressive Symptoms | 24hrs post-intervention | Self-reported depression (range: 0-27; higher scores = worse outcome) |
| Montgomery-Asberg Depression Rating Scale | 24hrs post-intervention | Clinician-rated depression (range: 0-60; higher scores = worse outcome) |
| fMRI Intrinsic Connectivity: Dorsal Attention Network | 24hrs post-intervention | functional connectivity normalized correlation values within dorsal attention network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
| fMRI Intrinsic Connectivity: Somatosensory Motor Network | 24hrs post-intervention | functional connectivity normalized correlation values within somatosensory motor network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
| fMRI Intrinsic Connectivity: Visual Network | 24hrs post-intervention | functional connectivity normalized correlation values within visual network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Dual Probe Video Task | infusion +24 hours (1 day) | attentional bias (proportion score) towards sad film clips (range: 0 to +1.0; higher score=greater attention bias towards sad films) |
| PROMIS Pain Interference Score | 1-hour post-infusion | PROMIS Pain Interference Short Form scale T-score (range=0-100; higher score=worse pain) |
| PROMIS Pain Intensity Score | 1-hour post-infusion | PROMIS Pain Intensity Short Form scale T-score (range=0-100; higher score=worse pain) |
| Pain Rating Via Quantitative Sensory Testing | 1-hour post-infusion | Pain rating obtained from Quantitative Sensory Testing by mechanical temporal summation (range: 0-10; higher score=more pain) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intravenous Ketamine Open-label ketamine infusion
Intravenous Ketamine: Single infusion of intravenous racemic ketamine (0.5mg/kg over 40min) | 15 |
| Total | 15 |
Baseline characteristics
| Characteristic | Intravenous Ketamine |
|---|---|
| Age, Continuous | 33.47 years STANDARD_DEVIATION 11.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Montgomery-Asberg Depression Rating Scale | 30.20 score on a scale STANDARD_DEVIATION 9.29 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 14 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
fMRI Intrinsic Connectivity: Default Mode Network
functional connectivity normalized correlation values within default mode network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Default Mode Network | 0.40 units on a scale | Standard Deviation 0.11 |
Primary
fMRI Intrinsic Connectivity: Frontoparietal Control Network
functional connectivity normalized correlation values within frontoparietal control network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Frontoparietal Control Network | 0.47 units on a scale | Standard Deviation 0.14 |
Primary
fMRI Intrinsic Connectivity: Limbic Network
functional connectivity normalized correlation values within limbic network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Limbic Network | 0.44 units on a scale | Standard Deviation 0.1 |
Primary
fMRI Intrinsic Connectivity: Salience Network
functional connectivity normalized correlation values within salience ventral attentional network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Salience Network | 0.53 units on a scale | Standard Deviation 0.13 |
Secondary
fMRI Intrinsic Connectivity: Dorsal Attention Network
functional connectivity normalized correlation values within dorsal attention network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Dorsal Attention Network | 0.54 units on a scale | Standard Deviation 0.11 |
Secondary
fMRI Intrinsic Connectivity: Somatosensory Motor Network
functional connectivity normalized correlation values within somatosensory motor network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Somatosensory Motor Network | 0.69 units on a scale | Standard Deviation 0.1 |
Secondary
fMRI Intrinsic Connectivity: Visual Network
functional connectivity normalized correlation values within visual network (range: -1 to +1; larger value = stronger connectivity, smaller value = weaker connectivity)
Time frame: 24hrs post-intervention
Population: All participants who received a ketamine infusion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | fMRI Intrinsic Connectivity: Visual Network | 0.60 units on a scale | Standard Deviation 0.08 |
Secondary
Hamilton Depression Rating Scale (Modified Score)
Clinician-rated depression (range: 0-52; higher scores = worse outcome)
Time frame: 24hrs post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Hamilton Depression Rating Scale (Modified Score) | 7.53 score on a scale | Standard Deviation 3.89 |
Secondary
Hamilton Depression Rating Scale (Modified Score)
Clinician-rated depression (range: 0-52; higher scores = worse outcome)
Time frame: 5 days post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Hamilton Depression Rating Scale (Modified Score) | 11.07 score on a scale | Standard Deviation 7.07 |
Secondary
Hamilton Depression Rating Scale (Modified Score)
Clinician-rated depression (range: 0-52; higher scores = worse outcome)
Time frame: 12 days post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Hamilton Depression Rating Scale (Modified Score) | 13.07 score on a scale | Standard Deviation 8 |
Secondary
Montgomery-Asberg Depression Rating Scale
Clinician-rated depression (range: 0-60; higher scores = worse outcome)
Time frame: 24hrs post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Montgomery-Asberg Depression Rating Scale | 11.80 score on a scale | Standard Deviation 7.55 |
Secondary
Montgomery-Asberg Depression Rating Scale
Clinician-rated depression (range: 0-60; higher scores = worse outcome)
Time frame: 12 days post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Montgomery-Asberg Depression Rating Scale | 19.93 score on a scale | Standard Deviation 13.57 |
Secondary
Montgomery-Asberg Depression Rating Scale
Clinician-rated depression (range: 0-60; higher scores = worse outcome)
Time frame: 5 days post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Montgomery-Asberg Depression Rating Scale | 15.00 score on a scale | Standard Deviation 10.45 |
Secondary
Quick Inventory of Depressive Symptoms
Self-reported depression (range: 0-27; higher scores = worse outcome)
Time frame: 24hrs post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Quick Inventory of Depressive Symptoms | 6.87 score on a scale | Standard Deviation 4.6 |
Secondary
Quick Inventory of Depressive Symptoms
Self-reported depression (range: 0-27; higher scores = worse outcome)
Time frame: 5 days post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Quick Inventory of Depressive Symptoms | 6.79 score on a scale | Standard Deviation 4.09 |
Secondary
Quick Inventory of Depressive Symptoms
Self-reported depression (range: 0-27; higher scores = worse outcome)
Time frame: 12 days post-intervention
Population: All participants who were assigned to the arm and were willing and able to complete this specific measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intravenous Ketamine | Quick Inventory of Depressive Symptoms | 9.71 score on a scale | Standard Deviation 5.59 |
Other Pre-specified
Dual Probe Video Task
attentional bias (proportion score) towards sad film clips (range: 0 to +1.0; higher score=greater attention bias towards sad films)
Time frame: infusion +24 hours (1 day)
Other Pre-specified
Pain Rating Via Quantitative Sensory Testing
Pain rating obtained from Quantitative Sensory Testing by mechanical temporal summation (range: 0-10; higher score=more pain)
Time frame: 1-hour post-infusion
Other Pre-specified
PROMIS Pain Intensity Score
PROMIS Pain Intensity Short Form scale T-score (range=0-100; higher score=worse pain)
Time frame: 1-hour post-infusion
Other Pre-specified
PROMIS Pain Interference Score
PROMIS Pain Interference Short Form scale T-score (range=0-100; higher score=worse pain)
Time frame: 1-hour post-infusion