Bipolar Disorder
Conditions
Brief summary
This study is a 4-month open-label study of lithium in the acute treatment of patients with bipolar I or II disorder. Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels \> 0.6 mEq/L. Blood samples are collected at baseline and at the end of study. Analyses of 45 molecule expressions in mononuclear blood cells at baseline and endpoint will be carried out after the completion of study. Fifty patients meeting Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) criteria for bipolar I or II will be enrolled.
Interventions
DRUGLithium
Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels \> 0.6 mEq/L
Sponsors
CellPrint Biotechnology
National Alliance for Research on Schizophrenia and Depression
Keming Gao
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
For inclusion in this study, subjects must meet all of the following criteria: 1. Able to provide informed consent before beginning any study-specific procedures; 2. Male or female, 18-70 years old; 3. Meets current DSM-5 criteria for bipolar I or II disorder as assessed by the The M.I.N.I. International Neuropsychiatric Interview (MINI); 4. Any symptomatic phase of bipolar I or II disorder including, depressive, manic, mixed or hypomanic 5. Global Clinical Impression-Severity for Bipolar Disorder (CGI-S-BD) ≥3; 6. Willing to take lithium; 7. If a sexually active female of childbearing potential, be using a reliable method of contraception; 8. Women with reproductive potential must have a negative urine pregnancy test; 9. Willing to have blood drawn:
Exclusion criteria
Any of the following is regarded as a criterion for exclusion from the study: 1. Unwilling to comply with study requirements; 2. Renal impairment (serum creatinine \>1.5 mg/dL); 3. Thyroid stimulating hormone (TSH) over \>20% above the upper normal limit (participants maintained on thyroid medication must be euthyroid for at least 3 months before Visit 1; 4. Other contraindication to lithium, 5. Patients who have had severe adverse reaction to Lithium; 6. Patients who require inpatient care; 7. Drug/alcohol dependence requiring immediate acute detoxification; 8. Pregnancy as determined by serum pregnancy test or breastfeeding; 9. History of nonresponse to lithium at doses ≥ 900 mg/d for ≥ 8 weeks; 10. Unwilling to have blood drawn 11. Patients with chronic medical conditions such as diabetes, coronary artery disease, immune diseases, infectious diseases and neurological disorders; 12. Active suicidal ideation with a plan or intent, a suicide attempt within past 6 months or more than 2 suicide attempts within the past 2 years. 13. Currently on lithium
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Baseline and Week 16 | Molecule expression is measured as a function of relative fluorescence intensity. The number derives from a photomultiplier tube which essentially counts photons. Higher numbers mean a higher intensity. The values in the results tables represents change in fluorescence intensity between Baseline and Week 16 across various molecules of interest and compares responders (those who experience a \>=50% decrease in mood symptom severity between baseline and week 16) and non responders (those who did NOT experience a \>=50% decrease in mood symptom severity between baseline and week 16). The rows represent the various molecules that were analyzed. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lithium Lithium: Eligible patients will receive lithium 300 mg twice daily and titrated in 300 mg increments every 7 days as tolerated to levels \> 0.6 mEq/L | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Lack of Efficacy | 3 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Pregnancy | 1 |
| Overall Study | Subject moved | 1 |
| Overall Study | Withdrawal by Subject | 4 |
Baseline characteristics
| Characteristic | Lithium |
|---|---|
| Age, Continuous | 38.9 years STANDARD_DEVIATION 12.99 |
| Bipolar Diagnosis Bipolar I Disorder | 17 Participants |
| Bipolar Diagnosis Bipolar II Disorder | 7 Participants |
| Lifetime Attention Deficit Hyperactivity Disorder (ADHD) Diagnosis | 14 Participants |
| Lifetime Generalized Anxiety Disorder (GAD) Diagnosis | 16 Participants |
| Lifetime Social Phobia Diagnosis | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 7 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 | 16 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 20 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium
Molecule expression is measured as a function of relative fluorescence intensity. The number derives from a photomultiplier tube which essentially counts photons. Higher numbers mean a higher intensity. The values in the results tables represents change in fluorescence intensity between Baseline and Week 16 across various molecules of interest and compares responders (those who experience a \>=50% decrease in mood symptom severity between baseline and week 16) and non responders (those who did NOT experience a \>=50% decrease in mood symptom severity between baseline and week 16). The rows represent the various molecules that were analyzed.
Time frame: Baseline and Week 16
Population: While we planned to analyze \~45 molecules of interest, poor quality of antibodies to some proteins \& financial limitations limited us to only 28 proteins. The number of participants analyzed for protein expression differs from baseline characteristic and varies below as not all subjects had high enough levels of a particular protein to be analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | mTor | 22.87 fluorescence intensity | Standard Deviation 6.41 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | HMGB1 | 23.18 fluorescence intensity | Standard Deviation 8.69 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PKA C-a | 24.51 fluorescence intensity | Standard Deviation 5.69 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | TNFAIP3 | 33.74 fluorescence intensity | Standard Deviation 6.16 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Bcl-2 A1 | 1.37 fluorescence intensity | Standard Deviation 0.2 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PDEB4 | 28.15 fluorescence intensity | Standard Deviation 9.12 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | BDNF | 37.78 fluorescence intensity | Standard Deviation 6.72 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | TPH1 | 7.13 fluorescence intensity | Standard Deviation 1.04 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | GSK-3b | 20.89 fluorescence intensity | Standard Deviation 7.88 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | IRS2 | 25.29 fluorescence intensity | Standard Deviation 5.64 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | XBP1 | 1.11 fluorescence intensity | Standard Deviation 0.36 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PKC theta | 33.8 fluorescence intensity | Standard Deviation 7.11 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | MARCKS | 1.32 fluorescence intensity | Standard Deviation 0.35 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-Fyn Yes | 12.49 fluorescence intensity | Standard Deviation 4.46 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-GSK 3b | 4.01 fluorescence intensity | Standard Deviation 0.78 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Bcl-2 | 39.72 fluorescence intensity | Standard Deviation 6.89 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-GSK 3ab | 2.29 fluorescence intensity | Standard Deviation 0.64 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-CREB | 30.78 fluorescence intensity | Standard Deviation 4.34 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Fyn | 33.01 fluorescence intensity | Standard Deviation 5.42 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | iNOS | 24.51 fluorescence intensity | Standard Deviation 4.38 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Timeless | 1.41 fluorescence intensity | Standard Deviation 0.12 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | BAK | 11.16 fluorescence intensity | Standard Deviation 2.08 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PGM1 | 30.96 fluorescence intensity | Standard Deviation 4.57 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | NR3C1 | 7.33 fluorescence intensity | Standard Deviation 2.16 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | NFKB p-P65 | 15.03 fluorescence intensity | Standard Deviation 6.01 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PPAR g | 21.90 fluorescence intensity | Standard Deviation 4.31 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Calmodulin | 34.44 fluorescence intensity | Standard Deviation 5.68 |
| Lithium Non Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | NLRP3 | 30.73 fluorescence intensity | Standard Deviation 5.66 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Calmodulin | 31.86 fluorescence intensity | Standard Deviation 7.7 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | NLRP3 | 26.00 fluorescence intensity | Standard Deviation 7.25 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PDEB4 | 27.31 fluorescence intensity | Standard Deviation 5.78 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | BAK | 11.50 fluorescence intensity | Standard Deviation 2.88 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-Fyn Yes | 13.33 fluorescence intensity | Standard Deviation 6.44 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | HMGB1 | 22.61 fluorescence intensity | Standard Deviation 6.58 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | IRS2 | 24.06 fluorescence intensity | Standard Deviation 8.71 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-CREB | 30.46 fluorescence intensity | Standard Deviation 6.55 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PPAR g | 21.13 fluorescence intensity | Standard Deviation 5.62 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | TNFAIP3 | 31.17 fluorescence intensity | Standard Deviation 6.64 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | TPH1 | 7.23 fluorescence intensity | Standard Deviation 2.47 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PKC theta | 35.81 fluorescence intensity | Standard Deviation 8.71 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Bcl-2 | 35.87 fluorescence intensity | Standard Deviation 8.94 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | iNOS | 24.54 fluorescence intensity | Standard Deviation 7.54 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | NR3C1 | 6.69 fluorescence intensity | Standard Deviation 2.64 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | mTor | 21.07 fluorescence intensity | Standard Deviation 8.6 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PKA C-a | 23.93 fluorescence intensity | Standard Deviation 7.08 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Bcl-2 A1 | 1.19 fluorescence intensity | Standard Deviation 0.3 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | BDNF | 34.00 fluorescence intensity | Standard Deviation 7.44 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | GSK-3b | 19.49 fluorescence intensity | Standard Deviation 6.47 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | XBP1 | 0.96 fluorescence intensity | Standard Deviation 0.2 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | MARCKS | 1.28 fluorescence intensity | Standard Deviation 0.54 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-GSK 3b | 4.11 fluorescence intensity | Standard Deviation 1.54 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | p-GSK 3ab | 1.93 fluorescence intensity | Standard Deviation 0.55 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Fyn | 30.24 fluorescence intensity | Standard Deviation 6.44 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | Timeless | 1.42 fluorescence intensity | Standard Deviation 0.4 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | PGM1 | 28.58 fluorescence intensity | Standard Deviation 6.64 |
| Lithium Responders | Change in Expression of ~45 Molecules in Blood Cells of Patients With Bipolar I or II Disorder Being Treated With Lithium | NFKB p-P65 | 14.58 fluorescence intensity | Standard Deviation 8.01 |