Clinical trial NCT03902613
Conditions: Bipolar Depression
Sponsor: New York State Psychiatric Institute
Start date: 2019-02-07; Completion date: 2019-08-01
Enrollment: 1 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The goal of this project is to understand what causes bipolar disorder and how medications treat bipolar depression. Particularly, the project focuses on the importance of dopamine signaling in the process. Participants will have two different brain scans (MRI and PET scan). They will also have treatment for your depression with an FDA approved medication, lurasidone (Latuda). The study is funded by the Columbia University Irving Institute to improve the treatment of bipolar disorder.

Detailed description:

Arms: arm 1: Open-label treatment with lurasidone within the dose range of 20-60 mg daily
Interventions: intervention 1: Lurasidone
Intervention descriptions: intervention 1: Participant will have an open label trial of lurasidone for eight weeks.

Protocol documents:
Prot_SAP_000.pdf: 
 
 
 
 
 
 
 
 
 
Research Protocol: 18F-DOPA PET to Elucidate the Antidepressant Mechanism of Lurasidone 
in Bipolar Disorder 
9/17/2019 
 
 
 
 
 
 
 
 
 
 
 
 


Recruitment Procedures 
Patients will be recruited through referrals from treating outpatient psychiatrists, or from clinics 
at Columbia University. Advertisements will be placed through the Columbia University website 
including the "RecruitMe" site and on advertising sites such as Craig’s List. A website that 
describes the study will be created. Messages will be posted on email list-serves of mental health 
clinicians describing the study and asking for referrals. Subjects will be recruited by Depression 
Evaluation Service members through IRB#6669R. 
Study staff and investigators will contact subjects who respond to advertising efforts to screen 
and recruit eligible individuals. For clinical patients at Columbia, only subjects who the clinical 
staff has identified as appropriate will be approached. The clinical staff will first ask the patient 
if he or she can be approached by research staff. Only if the subject agrees to be approached will 
the staff from this study do so. All potential subjects will be given the telephone number of the 
research coordinators who will discuss the purpose and procedures of the research and screen the 
subjects for potential eligibility.  
Texts of written materials to be distributed via advertisements and websites will be submitted to 
the IRB for approval before they are distributed. 
1. Initial screening will be completed as detailed in IRB#6879R or IRB#6669R.  
2. If eligible, subjects will be asked to sign the consent form for IRB# 4815 (Sublette). 
Participants will then be given a physical exam, laboratory test (via blood draw) and psychiatric 
examinations as performed under IRB#4815. IRB#4815 allows for clinical assessments, a 
medical screening for significant illness, a screening for drugs of abuse, a developmental history 
and acquisition of blood samples for genetic analyses. IRB#4815 allows for the above 
procedures so that subjects can enter any of several different types of studies and protocols.  
3. If eligible for IRB#4815, subjects will be given a detailed verbal explanation of this study by a 
research psychiatrist. During the consent process, the consenting psychiatrist will obtain a history 
of participants' past radiation exposure. Participants will then give written informed consent if 
they choose to participate in the study.  
Inclusion Criteria 
Criterion 
Method of Assessment 
1)Ability to provide informed consent 
Clinical interview 
2) Diagnosis of bipolar I disorder, bipolar 2 disorder or 
bipolar disorder NOS and currently meeting criteria for a 
major depressive episode 
DSM-IV by means of SCID 
3) Depression of sufficient severity to score at least 16 on the 
first 17 items of the Hamilton Depression Rating Scale 
including the atypical depression items addendum 
Hamilton Depression Rating 
Scale 
4) Age 18-50 years old 
Clinical interview 


5) Patients who were on psychiatric medication at 
presentation will have failed that regimen, as defined as not 
achieving at least partial remission after an adequate dose of 
medication for at least six weeks.  Benzodiazepines and 
hypnotics are allowed throughout the study 
Clinical interview 
6) Females of child-bearing potential must be willing to use 
an acceptable method of birth control throughout the study: 
abstinence, birth control pill, male condom, IUD, depo-
provera, Norplant, male sterilization or female sterlization 
Clinical interview 
7) Subject is likely to tolerate medication washout if 
indicated 
Clinical interview 
8) Must be enrolled in IRB#4815 
Review of records 
Exclusion criteria 
Criterion 
Method of Assessment 
1)Diagnosis of any other major psychiatric disorders such as 
schizoaffective disorder, current psychotic depression, or 
current drug or alcohol abuse (within two months before the 
study) or recent drug or alcohol dependence (within six 
months before the study); anorexia nervosa or bulimia 
nervosa within in the last year; Meet DSM-IV criteria for 
manic episode at the time of screening  
As defined by DSM-IV by 
means of SCID; urine drug 
screen  
 
2)Previous failed trial of lurasidone, defined by at leastv six 
weeks of treatment at the dose of 20 mg per day or more. 
Experienced intolerable side effects of lurasidone in the past. 
Taking any medications that are contraindicated with 
lurasidone unless there is a plan to stop these as part of the 
washout.  
Clinical interview 
3)History of clinical deterioration when any of the 
medications that the patient is taking at presentation have 
been discontinued in the past if they will be discontinued as 
part of the washout. 
Clinical interview 
4)First-degree family history of schizophrenia if the subject 
is less than 33 years old.  
Clinical interview 
5)Significant active physical illness, including blood 
dyscrasias, lymphomas, hypersplenism, endocrinopathies, 
renal failure, chronic obstructive lung disease, autonomic 
neuropathies, peripheral vasucalar disease, malignancy, 
neuromuscular disorder or tardive dyskinesia. Any medical 
diagnoses that would be a contraindication to lurasidone 
treatment. Hemoglobin <11 in females or <13 in males  
Medical history by a 
physician, physical exam, 
screening lab tests (chemistry 
panel [SMAC20], CBC, HCG 
test for pregnancy, urinalyzsis 
and TSH under IRB#4815  
 
6)Actively suicidal, as defined by expressive ideation with a 
plan for suicide or develops suicidal ideation that requires 
immediate medical or treatment intervention 
Clinical interview and score of 
5 or greater on CSSRS  


7)Pregnancy, abortion or miscarriage in the two months prior 
to enrollment or plans to conceive during the course of the 
study participation  
Clinical interview and serum 
pregnancy test at screening 
under IRB#4815  
8)Lactating women 
Clinical interview 
9)ECT within the past six months 
Clinical interview and chart 
review 
10)Subjects who endorse a history of prior head trauma and 
score 1.5 standard deviations below the mean of Trailmaking 
A & B 
Clinical interview and 
trailmaking A & B as needed  
 
11)Metal implants, pacemaker, metal prostheses, metal 
orthodontic appliances or shrapnel in the body unless there is 
confirmation that the substance is MRI compatible  
Clinical interview; written 
confirmation from health care 
provider if warranted 
12)Current, past or anticipated exposure to radiation 
including  
a) Having been badged for radiation exposure in the 
workplace 
b) Clinical judgement that past lifetime radiation 
exposure is extensive enough to make exposure to 
PET scans in the current study inadvisable. 
c)  Participation in nuclear medicine protocols in the 
last year*  
* Subjects will be eligible, however if the injected dose and 
dosimetry of the radiotracer are known and the cumulative 
annual exposure of the previous study and this sutdy is lower 
than the annual limit fo research subjects defined by the 
FDA (21 CFR 361.1)  
Clinical interview 
Study team will check our 
database to ensure that the 
subject has not participated in 
an imaging study within our 
Division in the past year. 
13)History of claustrophobia that would prevent 
participation in imaging scans  
Clinical interview 
14)Obesity with weight >350 lbs or inability to fit into the 
MRI scanner  
Medical evaluation and testing 
at MRI suite if needed 
15)Inadequate understanding of English 
Clinical interview 
16)Concurrent anticoagulant or anti-platelet treatment 
including aspirin if it is needed daily 
Clinical interview 
Research Procedures 
`Medication Washout: If patients are eligible to participate in the study, and they are taking 
psychiatric medications at the time of recruitment, they will have the psychiatric medications 
tapered off. The patients will be off of all medications for three weeks before PET scanning. This 
medication-free treatment period is necessary to obtain imaging and clinical outcome data that 
are not significantly influenced by previous medications. The design will also allow us to 
measure the clinical response to lurasidone that is independent from an interaction with the 
previous medications. Patients will meet with a psychiatrist from MIND or DES at least weekly 


in person during this time. A CGI, HAM-D, YMRS, psychotic symptoms of BPRS and CSSRS 
will be performed at least weekly to detect new onset of manic symptoms or clinical 
deterioration. Only patients who still meet inclusion criterion of HAM-D>15, including atypical 
depression items addendum, at the clinical appointment one week before the scheduled PET scan 
will continue. 
Patients who no longer meet inclusion criteria at the end of the period, including those that are no 
longer sufficiently depressed, will not continue with imaging and will be offered up to 6 months 
of open label outpatient treatment.  
Frequency of Clinical Visits: Throughout the study, outpatients will meet with a treating MIND 
or DES psychiatrist at least once a week in-person. Subjects will do the washout on the 4 Center 
or 5 South unit if clinically warranted. Inpatients will be evaluated by their physician at least 
three times weekly. In addition, all inpatients are monitored at intervals on an around-the-clock 
basis by ward clinical staff. During the washout period, inpatients will generally see a 
psychiatrist daily, except for weekends and holidays.  
MRI Scans: All subjects will have an MRI of the brain to obtain information on brain structure to 
co- register PET data. MRI scans will be obtained at the NYSPI MRI facility using a 3.0 Tesla 
GE scanner. Females of child bearing potential will have a urine hcg test within 24 hours of the 
scan. Subjects will have the option of visiting the MRI suite before the scan to enter a mock 
(fake) MRI scanner. The mock MRI scanner has the same dimensions as the real scanner so it 
allows participants to experience what it is like to be inside the actual magnet. The purpose of 
this is to have the subject be as comfortable as possible before the actual scan. Patients will 
receive an MRI scan lasting not more than 30 minutes. Structural scans will include T1-weighted 
and diffusion tensor imaging sequences. The procedure will be immediately stopped if the 
participant reports significant distress.  
PET Imaging: Each subject will undergo two PET scans with [18F]DOPA at the David A. 
Gardner PET Center at 722 West 168th Street, New York, NY 10032. One scan will be before 
lurasidone is initiated and the second will be four weeks (+/- one week) after starting lurasidone. 
Patients will not eat within 12 hours of the PET scan with the exception of a low-protein meal 
more than four hours before the scan. A urine pregnancy test will be done on females on the day 
of each PET scan, before the scan, to assure that pregnancy has not occurred between the time of 
laboratory tests at screening, during which a serum pregnancy test is conducted, and the PET 
scan. Patients will be given 150 mg of carbidopa PO within 120 minutes of the radiotracer 
injection. Carbidopa is used to prevent AAAD decarboxylation of the radiotracer so that it is 
bioavailable to cross into the brain. The subject will have an intravenous line placed for 
radiotracer injection. An arterial line will be placed in the radial artery of the other arm by an 
experienced physician, Dr. Ragy Girgis. Jayamole Kannamkzhiyil, RN will be present during the 
scan until the arterial line is removed. An MD clinician from the MIND Division will be on the 
CUMC campus and avilable during the scan via telephone. If Ms. Kannakuzhiyil is not available, 
Dr. Jeffrey Miller or Dr. Lan will be present during the scan until the arterial line removed. 
Patients will have vital signs measured before radiotracer injection and after PET scan is 
complete. If there is an complication with the arterial line placement, including patient refusal at 
the time of scan, the scan will proceed without blood sampling.  


The subject will be placed in a supine position on the camera bench. A head holder will be used 
to decrease head movement during the scan. A low dose computer tomography scan will be used 
to obtain data for attenuation correction. 5 mCi or less of [18F]DOPA will be administered I.V. 
over about 60 seconds. The emission scan will be initiated at the time of injection and emission 
data will be obtained for 90 minutes or less. During the emission scan, arterial samples will be 
drawn at 10 second intervals for the first two minutes and every 30 seconds for the second two 
minutes using an automated blood sampler. Thereafter, manual samples will be drawn at 6, 8, 10, 
15, 20, 50, 75 and 90 minutes. Radioactivity in the plasma will be measured using a gamma 
counter. If the patients need to get up from the scanner for any reason, the low dose attenuation 
computer tomography scan will be repeated once only per PET scan. Patients will have a clinical 
check in with a study physician within 48 hours of the PET scan for safety evaluation that will 
include an administration of CSSRS. Patients will have a urine pregnancy test conducted after 
the PET scan within 2 weeks of the scan.  
Clinical Treatment: Open-label lurasidone will be taken by participants after a meal, beginning at 
20 mg daily for the first two weeks. At that time, the dose can be increased to 40 mg daily for 
two weeks. Dosage will be raised only if the participant is tolerating the medication and has not 
been rated "much improved" or "very much improved" on the CGI improvement scale for that 
week. At week 4, blood samples will be drawn to measure blood glucose and lipids for safety 
monitoring. Treatment will be up to 4 weeks or until the second PET scan. Study visits will be 
weekly with a MIND or DES psychiatrist, unless the participant is rated much improved at week 
four, in which case visits will be biweekly thereafter. Additional visits can be scheduled at the 
study doctor's discretion for purposes of clinical management. At each visit, the study 
psychiatrist will complete the MADRS, YMRS, CGI, CSSRS, psychotic symptoms of BPRS, 
and SAFETEE-GI. Patients will complete self-rating forms at each visit. Participants with a 
Clinical Global Improvement (CGI) score of 6 ("much worse") or 7 ("very much worse") on two 
consecutive weeks during the trial will be terminated early from the study. Patients without 
alcohol or benzodiazepine use disorder may receive benzodiazepines for insomnia or 
anxiety/agitation (maximum dose equivalent to 4 mg of lorazepam per day). All patients may 
also receive zolpidem or diphenhydramine for insomnia or agitation.  
Lurasidone and all laboratory tests will be provided for free of charge to the participant. 
Participants will receive six months of free outpatient treatment including the treatment obtained 
through this protocol, with treatment visits at least monthly.  
Emergency Procedures: A research psychiatrist will be available by cell phone at all times during 
the study. Patients requiring urgent admission at the time of a study visit will be brought to the 
CUMC Emergency Department by the study physician and if necessary, security assistance will 
be provided. The treating psychiatrist will arrange non-urgent hospital admissions, preferably to 
the NYSPI 5-South unit. If patients refuse hospitalization but the clinical team determines that 
this is needed, the team will arrange all necessary interventions including contacting the local 
crisis team, family or Emergency Medical Services.  
Patients lost to follow-up: Upon enrollment, patients will be asked to provide the name and 
phone number of at least two persons who will likely know their future whereabouts. These 
people will be contacted if the subject is lost to follow up.  


Criteria for Early Discontinuation 
1) Intolerable side effects of lurasidone  
2) Refusal to continue regimen and willingness to receive open treatment 3) DSM-IV criteria for 
a manic episode or score > 12 on the YMRS  
4) During the washout period, if subjects score a six (much worse) or seven (very much worse) 
on the CGI- I, the protocol will be discontinued. If the participants do not tolerate the washout 
because of marked agitation, severe anorexia such as inability to drink adequate amount of 
fluids, or suicidal ideation or behavior with plan or intent, the protocol will be discontinued. In 
these cases, subjects will be offered open clinical treatment.  
5) During the lurasidone treatment phase, if subjects score a six (much worse) or seven (very 
much worse) on the CGI-I for two consecutive weeks, the trial will be terminated early. If there 
is clinical reason to change to open treatment, such as onset of psychotic symptoms, manic 
symptoms of clinical concern, active suicidal ideation on two consecutive visits, the clinical team 
will evaluate whether the risks outweigh the benefits of continuing protocol.  
6) If the patient requests withdrawal for any reason.  
7) The PI judges that it is medically unwise to continue in the study, for example if the subjects 
are unable to comply with the study procedures and rules.  
Radiotracer Information 
Name of the radiolabeled drug/compound: [18F]DOPA 
Manufacturer and other information: [18F]DOPA will be synthesized by the David Gardner PET 
Center at CUMC. IND 140398 is to use [18F]DOPA with lurasidone (latuda) as per this PSF. 
Lurasidone (Latuda) will not be used in an off label manner, however.  
IND is approved IND# 140398.  IND is held by PI/CU Investigator Lan, Martin, MD  
Data Analysis Plan 
The aim of the analyses is to provide feasibility data for a larger grant application. We will 
visualize all data to assess for trends that are not detectable in standard statistical analyses due to 
the small power of this preliminary study.