Trial Outcomes & Findings for PET and MRI Brain Imaging of Bipolar Disorder (NCT NCT01880957)
NCT ID: NCT01880957
Last Updated: 2022-07-20
Results Overview
Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible. After eight weeks of medication treatment, the HDRS score will be reevaluated with the HDRS-24 (and rescanned with PET and MRI). Participants who have a 50% or greater decrease in their HDRS-24 score will be considered responders (to Lithium treatment).
COMPLETED
NA
76 participants
8 weeks
2022-07-20
Participant Flow
Dates of Recruitment: 11/2011 - 05/2017 Location: University Medical Centers (Columbia, Stony Brook University)
1. Inclusion/Exclusion Criteria must be met prior to beginning study protocols. 2. Wash-out Period: For participants in the patient group, all were required to be 3 weeks medication free before beginning the study.
Participant milestones
| Measure |
Patients With Depression
Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode
Lithium
|
Healthy Volunteers
Participants in this group underwent baseline assessment for Hamilton Depression Rating Scale and Baseline PET and MRI Imaging. No treatment was provided for this group.
|
|---|---|---|
|
Overall Study
STARTED
|
47
|
29
|
|
Overall Study
COMPLETED
|
19
|
29
|
|
Overall Study
NOT COMPLETED
|
28
|
0
|
Reasons for withdrawal
| Measure |
Patients With Depression
Patients in this condition will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode
Lithium
|
Healthy Volunteers
Participants in this group underwent baseline assessment for Hamilton Depression Rating Scale and Baseline PET and MRI Imaging. No treatment was provided for this group.
|
|---|---|---|
|
Overall Study
Diagnosis: Unipolar Depression
|
12
|
0
|
|
Overall Study
Lost to Follow-up
|
11
|
0
|
|
Overall Study
Poor Tolerance to Lithium/Declined Treatment
|
5
|
0
|
Baseline Characteristics
PET and MRI Brain Imaging of Bipolar Disorder
Baseline characteristics by cohort
| Measure |
Patients With Depression
n=31 Participants
Patients with Bipolar depression will receive lithium administered as follows: Day 1, 2 and 3, 300 mg bid; Days 4-7 lithium 300 qam and 600 qhs. Lithium level will be checked as close to Day 7 as possible and titrated to a therapeutic plasma level of 0.8-1.2 mEq/l. Subjects will not undergo lithium monotherapy if they have a documented history of at least two failed trials of lithium of at least 4 weeks duration with therapeutic blood levels for a major depressive episode
Lithium
|
Healthy Volunteers
n=23 Participants
Participants in this group underwent baseline assessment for Hamilton Depression Rating Scale and Baseline PET and MRI Imaging. No treatment was provided for this group.
|
Total
n=54 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
31 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
54 Participants
n=206 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=99 Participants
|
12 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=99 Participants
|
11 Participants
n=107 Participants
|
27 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
23 Participants
n=99 Participants
|
16 Participants
n=107 Participants
|
39 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Hamilton Depression Rating Sale
|
26.19 units on a scale
STANDARD_DEVIATION 5.86 • n=99 Participants
|
1.62 units on a scale
STANDARD_DEVIATION 2.10 • n=107 Participants
|
16.71 units on a scale
STANDARD_DEVIATION 13.27 • n=206 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: Pre-to-Post lithium treatment change in HDRS Score
Patients will have a Hamilton Depression Rating Scale-24 (HDRS) score obtained at baseline. Minimum score 0, maximum possible score 75; the higher the score on the scale, the more severe the degree of depression. Participants must have an HDRS score of at least 15 to be eligible. After eight weeks of medication treatment, the HDRS score will be reevaluated with the HDRS-24 (and rescanned with PET and MRI). Participants who have a 50% or greater decrease in their HDRS-24 score will be considered responders (to Lithium treatment).
Outcome measures
| Measure |
Patients With BPD
n=19 Participants
Participants in this group included patients with bipolar depression who were subsequently treated with Lithium. Following baseline PET and MRI scans, treatment was initiated with lithium monotherapy. In brief: days 1-3: 300mg 2x/day, days 4-7: 300mg every morning and 600mg every night; titration to a therapeutic plasma level of 0.8-1.2 mEq/l. Following eight weeks of treatment, patients were rescanned with PET and MRI and reassessed with the HDRS-24.
|
Prediction by Pre-treatment 5-HT1A
Data analysis to determine whether pre-treatment 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
Combinatorial Prediction Using Pre-Treatment 5-HTT & 5-HT1A
Data analysis to determine whether pre-treatment 5-HTT \& 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
|---|---|---|---|
|
Post-Lithium Treatment Hamilton Depression Rating Scale (HDRS)
|
-44.49 Percent Change in HDRS-24 Score
Standard Deviation 34.17
|
—
|
—
|
PRIMARY outcome
Timeframe: 8 WeeksPopulation: Remission status prediction by groups: accuracy, specificity, and sensitivity. The analyzed population here must have completed both pre- and post-treatment scans for BOTH 5-HTT and 5-HT1A and have 8 weeks of HDRS-24 followup so the predictive power of each individual tracer could be assessed as well as the combination of the two tracers. This is a smaller population that each tracer individually or the outcome of the HDRS-24 scale alone.
Outcome measures were generated following LASSO linear regression analysis using pretreament HDRS-24 AND.. 1. pre-treatment 5-HTT OR 2. pretreatment 5-HT1A OR 3. the combination of both 5-HTT and 5-HT1A binding potential * to predict post-treatment response defined by a dichotomous remission status variable (remitter vs. non-remitter, where remitter is defined a priori by HDRS-24 \<10 post-treatment and a reduction of greater than or equal to 50% in HDRS-24 pre-to-post treatment). Outcome measure is reported as percent accuracy, sensitivity, or specificity in predicting remitter status outcomes.
Outcome measures
| Measure |
Patients With BPD
n=14 Participants
Participants in this group included patients with bipolar depression who were subsequently treated with Lithium. Following baseline PET and MRI scans, treatment was initiated with lithium monotherapy. In brief: days 1-3: 300mg 2x/day, days 4-7: 300mg every morning and 600mg every night; titration to a therapeutic plasma level of 0.8-1.2 mEq/l. Following eight weeks of treatment, patients were rescanned with PET and MRI and reassessed with the HDRS-24.
|
Prediction by Pre-treatment 5-HT1A
n=14 Participants
Data analysis to determine whether pre-treatment 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
Combinatorial Prediction Using Pre-Treatment 5-HTT & 5-HT1A
n=14 Participants
Data analysis to determine whether pre-treatment 5-HTT \& 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
|---|---|---|---|
|
Prediction of Treatment Response
Prediction Accuracy = True positive + negative divided by the sum of true + false positive/negative
|
71.4 Percentage
|
85.7 Percentage
|
84.6 Percentage
|
|
Prediction of Treatment Response
Prediction Specificity = True negatives divided by the sum of true negative and false positive
|
77.8 Percentage
|
87.5 Percentage
|
87.5 Percentage
|
|
Prediction of Treatment Response
Prediction Sensitivity= True positives divided by the sum of true positive and false negative
|
60 Percentage
|
80 Percentage
|
60 Percentage
|
SECONDARY outcome
Timeframe: 8 WeeksPopulation: Comparison of mean binding potential across patients pre-treatment, post-treatment, and controls.
Differences in mean of 5-HTT binding potential between patients with depression pre-treatment, post-treatment, compared to healthy volunteers. Broadly, binding potential is defined as the ratio of the tracer concentration in tissue to the free plasma concentration. It is a measure of the density of "available" targets (e.g. 5-HTT) \& the affinity of the ligand (tracer) to that target.
Outcome measures
| Measure |
Patients With BPD
n=23 Participants
Participants in this group included patients with bipolar depression who were subsequently treated with Lithium. Following baseline PET and MRI scans, treatment was initiated with lithium monotherapy. In brief: days 1-3: 300mg 2x/day, days 4-7: 300mg every morning and 600mg every night; titration to a therapeutic plasma level of 0.8-1.2 mEq/l. Following eight weeks of treatment, patients were rescanned with PET and MRI and reassessed with the HDRS-24.
|
Prediction by Pre-treatment 5-HT1A
n=19 Participants
Data analysis to determine whether pre-treatment 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
Combinatorial Prediction Using Pre-Treatment 5-HTT & 5-HT1A
n=14 Participants
Data analysis to determine whether pre-treatment 5-HTT \& 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
|---|---|---|---|
|
Group Differences in 5-HTT Binding Potential
Amygdala
|
198.56 Weighted Mean Binding Potential
Standard Error 27.64
|
116.94 Weighted Mean Binding Potential
Standard Error 28.73
|
166.73 Weighted Mean Binding Potential
Standard Error 61.75
|
|
Group Differences in 5-HTT Binding Potential
Grey Matter of Cerebellum
|
93.27 Weighted Mean Binding Potential
Standard Error 17.86
|
88 Weighted Mean Binding Potential
Standard Error 1.87
|
88.70 Weighted Mean Binding Potential
Standard Error 21.71
|
|
Group Differences in 5-HTT Binding Potential
Midbrain
|
264.82 Weighted Mean Binding Potential
Standard Error 32.47
|
81.73 Weighted Mean Binding Potential
Standard Error 18.59
|
181.13 Weighted Mean Binding Potential
Standard Error 90.20
|
|
Group Differences in 5-HTT Binding Potential
Anterior Cingulate
|
131.80 Weighted Mean Binding Potential
Standard Error 26.99
|
187.48 Weighted Mean Binding Potential
Standard Error 60.73
|
130.04 Weighted Mean Binding Potential
Standard Error 30.73
|
SECONDARY outcome
Timeframe: 8 WeeksPopulation: Comparison of mean binding potential across patients pre-treatment, post-treatment, and controls.
Differences in mean of 5-HT1A binding potential between patients with depression pre-treatment, post-treatment, compared to healthy volunteers. Broadly, binding potential is defined as the ratio of the tracer concentration in tissue to the free plasma concentration. It is a measure of the density of "available" targets (e.g. 5-HT1A) \& the affinity of the ligand (tracer) to that target.
Outcome measures
| Measure |
Patients With BPD
n=23 Participants
Participants in this group included patients with bipolar depression who were subsequently treated with Lithium. Following baseline PET and MRI scans, treatment was initiated with lithium monotherapy. In brief: days 1-3: 300mg 2x/day, days 4-7: 300mg every morning and 600mg every night; titration to a therapeutic plasma level of 0.8-1.2 mEq/l. Following eight weeks of treatment, patients were rescanned with PET and MRI and reassessed with the HDRS-24.
|
Prediction by Pre-treatment 5-HT1A
n=17 Participants
Data analysis to determine whether pre-treatment 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
Combinatorial Prediction Using Pre-Treatment 5-HTT & 5-HT1A
n=13 Participants
Data analysis to determine whether pre-treatment 5-HTT \& 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
|---|---|---|---|
|
Group Differences in 5-HT1A Binding Potential
Raphe Nucleus
|
8.91 Weighted Mean Binding Potential
Standard Error 3.15
|
9.62 Weighted Mean Binding Potential
Standard Error 1.79
|
8.57 Weighted Mean Binding Potential
Standard Error 2.58
|
|
Group Differences in 5-HT1A Binding Potential
Parahippocampal Gyrus
|
12.48 Weighted Mean Binding Potential
Standard Error 2.41
|
14.88 Weighted Mean Binding Potential
Standard Error 3.13
|
15.79 Weighted Mean Binding Potential
Standard Error 3.75
|
|
Group Differences in 5-HT1A Binding Potential
Amygdala
|
20.8 Weighted Mean Binding Potential
Standard Error 5.26
|
17.86 Weighted Mean Binding Potential
Standard Error 4.39
|
14.01 Weighted Mean Binding Potential
Standard Error 3.41
|
|
Group Differences in 5-HT1A Binding Potential
Hippocampus
|
27.06 Weighted Mean Binding Potential
Standard Error 8.40
|
30.17 Weighted Mean Binding Potential
Standard Error 7.84
|
28.39 Weighted Mean Binding Potential
Standard Error 7.73
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: Linear regression between change in PET binding potential pre and post treatment and treatment response.
Linear regression \& correlation to assess the relationship between between change in binding potential pre- to post treatment vs. treatment response
Outcome measures
| Measure |
Patients With BPD
n=14 Participants
Participants in this group included patients with bipolar depression who were subsequently treated with Lithium. Following baseline PET and MRI scans, treatment was initiated with lithium monotherapy. In brief: days 1-3: 300mg 2x/day, days 4-7: 300mg every morning and 600mg every night; titration to a therapeutic plasma level of 0.8-1.2 mEq/l. Following eight weeks of treatment, patients were rescanned with PET and MRI and reassessed with the HDRS-24.
|
Prediction by Pre-treatment 5-HT1A
n=13 Participants
Data analysis to determine whether pre-treatment 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
Combinatorial Prediction Using Pre-Treatment 5-HTT & 5-HT1A
Data analysis to determine whether pre-treatment 5-HTT \& 5-HT1A binding potential along with pre-treatment HDRS-24 predicted treatment response (remission status).
|
|---|---|---|---|
|
Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response
R-Squared: 5-HTT Midbrain
|
0.061 Percent Change in Binding Potential
|
NA Percent Change in Binding Potential
Region not analyzed for this tracer due to lack of target.
|
—
|
|
Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response
R-Squared: 5-HT1A Raphe
|
NA Percent Change in Binding Potential
Region not analyzed for this tracer due to lack of target.
|
0.086 Percent Change in Binding Potential
|
—
|
|
Relationship Between Change in 5-HTT or 5-HT1A Binding Potential Pre- to Post Treatment and Lithium Treatment Response
R-Squared: 5-HT1A Hippocampus
|
NA Percent Change in Binding Potential
Region not analyzed for this tracer due to lack of target.
|
0.073 Percent Change in Binding Potential
|
—
|
Adverse Events
Patients With Depression
Healthy Volunteers
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place