Clinical trial NCT01658150
Conditions: Schizophrenia Schizoaffective Disorder
Keywords: Cognition Schizophrenia Schizoaffective disorder
Sponsor: Icahn School of Medicine at Mount Sinai
Start date: 2012-09-01; Completion date: 2018-01-02
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to evaluate the use of the drug isradipine for cognitive enhancement in patients diagnosed with schizophrenia and schizoaffective disorder.

Detailed description:
The purpose of this study is to evaluate the use of the drug isradipine for cognitive enhancement in patients diagnosed with schizophrenia and schizoaffective disorder. Incomplete treatment response can be common in these disorders. While there are medications that are effective at treating positive symptoms, some other symptoms of the disorders are often left only partially treated (cognitive impairment and negative symptoms). This study will begin to address if the medication isradipine might help to treat some of the cognitive problems associated with schizophrenia and schizoaffective disorder. Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel. It is currently approved by the FDA for hypertension.

Arms: arm 1: open label
Interventions: intervention 1: isradipine
Intervention descriptions: intervention 1: Isradipine is a medication that acts by blocking a specific type of receptor in the brain called a calcium channel

Protocol documents:
Prot_SAP_000.pdf: 
A Molecular Approach to Treat Cognition in Schizophrenia: Ca2+ Channel 
Blockade
PI: Katherine Burdick
NCT01658150
Document Date: May 16, 2017


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
1 
Revised  9/2/14 
MSSM Protocol Template HRP-503a 
Instructions: 
1. Prepare a document with the following sections. Note that, depending on the nature of your research, 
certain sections below may not be applicable. Indicate N/A as appropriate, explaining where possible. 
2. For any items described in the sponsor’s protocol, grant application or other source documents 
submitted with the application, you may reference the title and page numbers of these documents rather 
than cutting and pasting into this document. Do NOT refer to any derived documents, such as the 
Sample Consent document, or other internal documents required with the submission. 
3.  If you reference page numbers, attach those pages to this protocol. 
4. When you write a protocol, keep an electronic copy. You will need to modify this copy when making 
changes. 
 
1) Objectives: 
In this project we propose to conduct a 4-week open label cognitive enhancement trial of 
isradipine in up to 80 stable outpatients with schizophrenia and schizoaffective disorder. 
 
The primary aim of this study is to evaluate the effects of the calcium channel antagonist, 
isradipine on cognitive dysfunction in patients with schizophrenia and schizoaffective 
disorder.  Incomplete treatment response is common. Cognitive impairment and negative 
symptoms persist in a majority of patients even when positive psychotic symptoms are 
well-controlled, and they account for a large proportion of the variance in explaining 
functional disability (Keefe et al. 2007). This has led to a focused effort to target the 
specific treatment of cognition in patients with schizophrenia (Green and Nuechterlein, 
2004), with somewhat limited success to date. 
 
Novel treatment options have been limited by an incomplete understanding of the 
biological etiology of schizophrenia; however, recent data from the field of genomics 
have provided insights into the molecular underpinnings of schizophrenia and its 
associated symptoms. The majority of genetic risk loci identified to date show trans-
disorder effects, increasing susceptibility across a broad range of neuropsychiatric 
disorders including schizophrenia and bipolar disorder (Williams et al. 2011; Purcell 
2009). One possible explanation for this overlap is that several of these genes are 
influencing risk via their effects on shared phenotypes such as neurocognitive 
dysfunction. One such example is a single nucleotide polymorphism (SNP; rs1006737) in 
the calcium channel gene, CACNA1C; initially associated with bipolar illness (Sklar et 
al. 2008; 2011; Ferriera et al 2008) but also linked with schizophrenia (Green et al. 2009; 
Nyegaard et al. 2010) and recurrent major depression (Green et al, 2009). The strength of 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
2 
Revised  9/2/14 
the association signal for CACNA1C in major mental illness is unambiguous and several 
subsequent studies have evaluated the effects of CACNA1C variation on neurocognitive 
capacity. 
2) Background 
CACNA1C rs1006737 has been shown to affect neural networks underlying reward and 
emotional processing (Bigos et al. 2010; Wessa et al. 2010), verbal fluency (Krug et al. 
2010), alerting and orienting aspects of attention (Thimm et al. 2011), and executive 
functions (Bigos et al. 2010). CACNA1C is responsible for coding the L-type voltage-
gated calcium channel Cav1.2, which has been shown to be involved in synaptic 
plasticity, learning and memory in an NMDA-independent manner (Woodside et al. 
2004; Moosmang et al. 2005; White et al. 2008) and CACNA1C knock-out mice show 
notable deficits in long term potentiation (Striessnig et al. 2006).  These convergent data 
suggest that variation within CACNA1C may play a critical role in the development of 
neurocognitive deficits associated with schizophrenia and may point toward a novel 
treatment strategy targeting calcium channel dysfunction for these disabling symptoms. 
 
Dysregulation of intracellular Ca2+ homeostasis and excess calcium signaling have been 
hypothesized to underlie multiple pathogenic processes in schizophrenia, including 
dopaminergic hyperactivity and hypofunction of the N-methyl-D-aspartate (NMDA) 
receptor (Bojarki et al. 2010). In selecting an intervention, we considered the numerous 
calcium-channel blockers that are widely utilized as anti-hypertensives; however, we 
chose isradipine for its specificity for the CaV1.2 channel subtype and its superior blood-
brain barrier penetrance.  
 
3) Setting of the Human Research 
The Icahn School of Medicine at Mount Sinai (ISMMS) site has ideal facilities for the 
proposed study. The research activities will be conducted in the Laboratory of 
Neurocognition located at 53-55 E. 96th Street, 1st floor suite. This space, completely 
renovated in 2014, consists of a seven-room suite with ample space for research staff, 
interview rooms, and an exam room.  
 
4) Resources Available to Conduct the Human Research 
The current study will be performed in the Department of Psychiatry, located at the Icahn 
School of Medicine at Mount Sinai (ISMMS).  Referrals will primarily come from 
Manhattan based Mount Sinai Health System  Outpatient Psychiatry Departments.  These 
will include the Mount Sinai Hospital, Beth Israel, and St. Luke’s Roosevelt. 
 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
3 
Revised  9/2/14 
5) Study Design 
a) Recruitment Methods 
Subjects will be recruited from the outpatient clinical services of the Mount Sinai Health 
System as described above.  Potentially eligible patients are identified by the patient’s 
clinical care provider (nurse practitioner and/or physician), who would then ask the 
patient’s permission for our research team to approach and explain the protocol.  A 
research team member will approach that individual and explain the study objectives, 
procedures, risks and benefits, and begin the informed consent process if the patient 
wishes to. We will also utilize IRB approved community based advertisements.  
b) Inclusion and Exclusion Criteria 
Inclusion criteria: 1. Age 18-60; 2. DSM-IV schizophrenia or schizoaffective diagnosis; 
3. Residual phase of illness criteria met at screen and baseline as defined by item scores 
of < 4 on each of the Brief Psychiatric Rating Scale (BPRS) hallucinatory behavior, 
unusual thought content, and conceptual disorganization items; 4. Hamilton Rating Scale 
for Depression (HRSD) < 12; 5. Baseline Clinician Administered Ratings Scale for 
Mania (CARS-M) score of <5; 6. Simpson Angus Scale (SAS) total score of < 6; 7. 
Treatment with at least one but no more than two stably-dosed second-generation 
antipsychotic medication (other than clozapine) for > 2 months and no changes planned 
over the 4-week study period. First generation antipsychotics and clozapine are thought 
to cause significant cognitive impairment. Initial baseline cognitive functioning will not 
be evaluated as inclusion/exclusion criterion because schizophrenia/schizoaffective 
disorder have a relatively cognitively homogeneous patient sample. We do not anticipate 
any subjects without cognitive impairment. We will cover for baseline performance to 
determine if degree of cognitive impairment at baseline is responsible for any change 
noted. 
Exclusion criteria: 1. History of CNS trauma, neurological disorder, ADHD, mental 
retardation, learning disability, or other non-schizophrenic cause of cognitive 
impairment; 2. DSM-IV diagnosis of substance abuse/dependence within 3 months or 
positive urine toxicology at screening that is not consistent with what participant 
reported. Substance abuse and dependence are determined based on an extremely 
comprehensive interview (the SCID), which evaluates lifetime history and current history 
of all substance use disorders. As per the protocol, DSM-IV diagnosis of substance abuse 
or dependence within 3 months will be exclusionary (not substance use); 3. Pregnant 
women or women of child bearing potential who are not using a medically accepted 
means of contraception (including oral contraceptive or implant, condom, diaphragm, 
spermicide, intrauterine device, tubal ligation, or partner with vasectomy) 4. Women who 
are breastfeeding; 5. Active, unstable medical problem that may interfere with cognition; 
6. Current treatment for hypertension; 7. Uncontrolled hypertension; 8. History of heart 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
4 
Revised  9/2/14 
disease; 9. Any drug known to interact with isradipine. 10. History of GI strictures; 11. 
Abnormal lab or ECG at screen. 12. Significant suicidal ideation at baseline (HRSD item 
3 > 2). Concomitant Medications: Practical and ethical considerations prevent an 
exclusive focus on medication-free patients; however, we will limit participation to 
individuals taking at least one and no more than 2 concomitant antipsychotic medications 
and we will exclude subjects who have received ECT within 12 months. Medication load 
will be incorporated as covariates in statistical analyses using chlorpromazine (CPZ) 
equivalents. 
c) Number of Subjects 
Up to 80 stable schizophrenia and schizoaffective patients will be recruited from the 
Mount Sinai Health System Outpatient Departments, and community advertisements. 
d) Study Timelines 
The recruitment and enrollment process will be active for approximately 24 months.  The 
anticipated final date for this study is 7/2017.  The patients will be informed of the length 
of the study, which will include 8 visits in total. There will be a screening visit, baseline 
visit when they will receive the study medication, a visit eight hours after the first dose of 
medication is taken (baseline) where blood pressure will be checked, 4 weeks of 
medication administration and weekly monitoring, and a visit eight hours after the dosage 
of the medication is increased (week 2) where blood pressure will be checked.  They will 
be informed of all of the study procedures for each week, including assessments and 
medical tests. 
e) Study Endpoints 
The primary endpoint related to the efficacy of isradipine will be cognitive enhancement 
measured by the MATRICS Consensus Cognitive Battery (MCCB).  The MCCB is 
accepted by the FDA as a primary outcome measure for registry trials of cognitive 
enhancement in schizophrenia. 
f) Procedures Involved in the Human Research 
All eligible subjects will undergo visits at screening, baseline (week 0), visit 8 hours after 
week 0, week 1, week 2, visit 8 hours after week 2, week 3, and week 4 (end of study). 
The parameters of study drug dosing are as follows: isradipine as utilized in this trial will 
be administered twice daily. Isradipine will be titrated as follows: baseline (week 0) 5 
mg/day BID; Week 2 increase to 10 mg/day BID if 5 mg was well-tolerated. Dosing will 
be flexible based on side effects with a maximum=10 mg/day. If 5 mg cannot be 
tolerated, the subject will be discontinued. Dosing was based on package labeling for 
hypertension and prior studies in Parkinson’s disease (Simuni et al. 2010). 
 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
5 
Revised  9/2/14 
Measures described in detail below: 
 
Safety Outcome Measures 
 The Side Effects Checklist (SEC; physician administered) and side effect 
self-report form – (all visits) 
 Vital signs including blood pressure (standing/supine – all visits) 
 Blood pressure check within 8 hours of first dose. Staff contact number 
will be given to subject in case there are any problems before the 8 hour 
BP check (week 0).  An additional blood pressure check 8 hours after 
increased dosage (week 2). 
 Electrocardiogram (ECG); chemistry panel and CBC via blood draw 
(approximately 2 TSP blood drawn); urinalysis (screening & week 4) 
 Urine toxicology (screening) 
 Urine pregnancy test for women of childbearing potential (baseline) 
 Abnormal Involuntary Movement Scale (AIMS) and Simpson Angus 
Scale (SAS) (all visits) 
 Beck Scale for Suicidal Ideation (SSI) and Columbia Suicide Severity 
Rating Scale (C-SSRS) (all visits) 
Clinical/Symptom Measures 
 Structured Clinical Interview for the DSM-IV (SCID-IV) (screening) 
 Symptom rating scales including the Brief Psychiatric Rating Scale 
(BPRS), the Scale for the Assessment of Negative Symptoms (SANS), the 
Hamilton Rating Scale for Depression (HRSD), the Clinical Global 
Impression Scale (CGI), the Clinician Administered Rating Scale for 
Mania (CARS-M) (all visits) 
Neurocognitive/Functional Measures 
 MATRICS Consensus Cognitive Battery* (baseline & week 4) 
 UCSD Performance Skills Assessment (UPSA) (baseline & week 4) 
 Quality of Life Scale (QoL) (baseline & week 4) 
 
 
 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
6 
Revised  9/2/14 
* Table 1. 
The MATRICS Consensus 
Cognitive Battery 
Domain 
Note/Description 
Category Fluency 
Speed of Processing 
Total animals in 60 seconds 
BACS Symbol Coding 
Speed of Processing 
Matching numbers to 
symbols 
Trail Making Test Part A 
Speed of Processing 
Dot-to-dot: Numbers only 
CPT-Identical Pairs 
Attention/Vigilance 
Computerized numeric 
stimuli 
Letter-Number Span 
Working Memory 
Recoding numbers and letters 
in order 
WMS-III Spatial Span 
Working Memory 
Visual sequence forward and 
backward 
Hopkins Verbal Learning (HVLT) 
Verbal Learning 
12 word list x 3 
Brief Visuospatial Memory Test 
(BVMT) 
Visual Learning 
6 designs to be drawn from 
recall 
NAB Mazes 
Reasoning & Prob Solving 
Pencil-paper maze solutions 
MSCEIT Managing Emotions 
Social Cognition 
Situational social judgments 
Additional Measures (“Plus”) 
--- 
--- 
Affective Go-no-go 
Affective Neuroscience 
Emotional modulation of 
inhibition 
Emotional Stroop 
Affective Neuroscience 
Affective Bias/Cognitive 
Control 
 
g) Specimen Banking 
 
N/A 
 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
7 
Revised  9/2/14 
h)  Data Management and Confidentiality 
If a participant agrees to be in this study, we will collect health information that identifies 
them, “Protected Health Information” (PHI). We may collect the results of tests, 
questionnaires and interviews. We may collect information from a patient’s medical 
record.  We will only collect information that is needed for the research. This information 
is described in the consent form. By signing the consent form a participant gives us 
permission (authorization) to collect, use and share their health information. 
Data collected will include questionnaires and assessments as described above in section 
(5f). Labs and tests will be done at the ISMMS laboratory and information sent to the PI, 
data for these will be stored in a binder which will be secured in a double locked fashion. 
Blood samples will be labeled with de-identified codes, which cannot be associated with 
individual subjects. PHI, such as patient name and DOB, will only be included in a 
separate file including the consent documents. All other data collected for the study will 
be de-identified and stored apart from PHI, identified by study number linked to PHI in a 
secure file. This data will be stored indefinitely. 
The PI will be responsible for receipt and transmission of study data and specimens. 
Quality control of the data collected will include double data entry and data quality check 
by investigators after each 5 subjects completed. 
 
Study staff will have access to data and records may be reviewed by the Mount Sinai 
School of Medicine Institutional Review or government agencies (i.e. NIH) in order to 
meet federal or state research regulations.  Please be aware that once private information 
is disclosed, it is subject to re-disclosure by the recipient and can no longer be considered 
protected.  If research records are used for decisions related to clinical care, then a 
participant has the right to review this information and to request changes. This is limited 
to information about their treatment, and does not include information related to 
procedures or tests that are for research purposes only. Participants may access this 
information only after the study analysis is complete.   
 
 
Data from this study may be used in medical publications or presentations.  The 
information will be de-identified so that individual subjects cannot be recognized and the 
information will no longer be considered PHI.  The information that is collected for 
research will be analyzed for many years and it is not possible to know how long this 
analysis and follow-up will take. Therefore, participants are allowing access to this 
information indefinitely. 
Subjects will only be identified with a numerical code in compliance with HIPAA 
regulations. Raw subject data will be secured in double locked physical control. Digitized 
raw data will be similarly de-identified using coding and will be secured on an MS SQL 
server with Windows integrated security.  


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
8 
Revised  9/2/14 
Data analysis plan is included below. All analyses will be based on an intent-to-treat 
sample of subjects who received at least one dose of isradipine. Since the missing values 
may be dependent on the observed outcomes, we assume the missing data mechanism to 
be missing at random, and hence a mixed models analysis will be used to assess the 
treatment effect of isradipine with fixed effects for week and first order autoregressive 
covariance structure to evaluate change over time for all of the primary outcome 
measures.  Cognitive measures will be handled differently, as these will only be collected 
at two time points – if missing data are substantial (or a complete visit is missing), 
subjects’ data will not/cannot be meaningfully analyzed. 
Primary Analyses will test the following hypotheses based on our specific aims: 
To determine the feasibility of 4 weeks of isradipine on cognitive outcomes in SZ. 
Hypothesis: We will successfully recruit up to 80 stable schizophrenia and 
schizoaffective patients 
 
To determine the safety of 4 weeks of isradipine on cognitive outcomes in SZ. 
Hypothesis: The frequency of new or worsened side effects (clinician-rated; self-
reported; lab-based) will not be significantly different from baseline to end of study visit. 
 
A Fisher exact test will compare time-points by frequencies of new or worsened 
(compared with baseline) side effect severity ratings – this will be done for all side 
effects assessed by the SEC. 
 
Differences on laboratory measures (chemistry panel, etc.) will be tested using repeated 
measures ANCOVA (baseline and week 4) and changes in vital signs (specifically blood 
pressure) will be assessed using mixed model ANCOVA, to incorporate data at each 
weekly visit. 
 
Differences on SAS and AIMS total scores will be examined by calculating the τ-b rank 
correlation between score and week for each subject and comparing the distribution of 
these trend scores with the Conover-Salsburg rank test.  
i) Provisions to Monitor the Data to Ensure the Safety of subjects 
Safety monitoring will be done on a patient by patient basis by the PI and the study 
physician on weekly visits. Side effects will be monitored closely and all AEs recorded. 
To increase safety, a blood pressure check will be done within 8 hours of this first dose 
(baseline). Staff contact number will be given to subject before the first dose in case there 
are any problems before the 8 hour BP check.  Additionally, a blood pressure check will 
be done within 8 hours of increasing the dosage (week 2).   


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
9 
Revised  9/2/14 
The PI will summarize all safety related outcomes after each set of 5 patients have 
completed the study and discuss these results with study physicians. This monitoring will 
be applied sooner than 5 patients if indicated, or if a SAE or unanticipated event occurs. 
All SAEs will be reported to the IRB within 24 hours and documented as per protocol. In 
the case that there are safety concerns from the PI or the IRB, this will be addressed in an 
ongoing manner. Independent of any SAEs, a Data Safety Monitoring Plan will be 
submitted to the IRB after the first 15 participants have been enrolled. 
j) Withdrawal of Subjects 
If they choose to consent to the study and are eligible to begin the trial, they will be 
closely monitored and will visit with the study coordinator and study physician.  Side 
effects will be rated weekly at each visit using an adverse events checklist completed by a 
study physician.  Subjects with an exacerbation of psychosis/depression/mania on a 2-
point CGI-change score will be discontinued and treated appropriately by the study 
physician.  Suicidal ideation will be assessed at each visit with the Beck (SSI) and the 
Columbia Suicide Severity Rating Scale (C-SSRS).  Significant suicidal ideation will be 
addressed immediately using the standard clinical response at ISMMS (evaluation at the 
walk-in clinic/psychiatric emergency room for potential need to hospitalize).  Subjects at 
risk for suicidal behavior will be discontinued. Subjects with any other clinical worsening 
as noted by study physician, and any instance of an SAE will be discontinued. In 
addition, subjects who exhibit any inability to follow the protocol with be discontinued 
and withdrawn from the study.  
To ensure orderly termination from the study, the study physician would meet with the 
subject to discuss termination and discontinuation of medication. Safety measures would 
be collected and a follow-up visit by phone would be scheduled to further ensure safe 
discontinuation. Discontinuing isradipine does not require a taper. We will schedule an 
in-person visit if necessary after the follow-up visit by phone to address any remaining 
concerns the subject may have.  
Subjects may withdraw from the study for any reason at any time by contacting the 
principal investigator or any of the research staff. It is also possible to withdraw 
permission for the use and disclosure of any protected information for research, but it 
must be done in writing to the principal investigator. In the event permission is 
withdrawn, information that was already collected may still be used if that information is 
necessary to complete the research study. 
6) Risks to Subjects 
During the informed consent process, subjects will be informed of the potential risks 
associated with the study. Isradipine has not been shown to induce or worsen psychosis in 
any of the published human data; nonetheless, symptoms may worsen in the course of the 
study. We will very closely monitor psychotic and affective symptoms on a weekly basis 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
10 
Revised  9/2/14 
throughout the study period using standardized rating scales described above in 5f). At 
each weekly visit the study physician will meet with the patients and conduct a thorough 
review of symptoms including psychosis, mood, and suicidal/homicidal ideation. If there 
is an acute worsening of symptoms the study clinicians will review the case with the PI 
(or will make an emergency decision as needed) to ensure that the subject receives 
emergency care or hospitalization. Participation in the study will be discontinued in any 
case of clear symptom worsening. Between weekly visits, the patients will have 
emergency contact information.  
Along with closely monitoring for symptom exacerbation, each visit with the study 
physician will entail a detailed side effect evaluation, which will include vital signs and a 
side effect checklist.  The most common side effects of isradipine include hypotension, 
edema, headache, dizziness, palpitations, fatigue, flushing, and constipation. Patients will 
be educated about the potential for hypotension and its symptoms, and blood pressure and 
symptoms will be measured at every visit. If the patient develops clinically significant 
hypotension (e.g., systolic blood pressure equal to or less than 90 mm Hg or diastolic 
equal to or less than 60 mm Hg, or if they experience significant associated symptoms), 
or if at any point in the study subsequent to baseline there is a blood pressure drop of 
20% or more from blood pressure at baseline, they will be discontinued from the study 
medication and excluded from the protocol. Rare side effects have also been reported 
including arrhythmias, syncope, severe hypotension or myocardial infarction. The 
informed consent process will alert subjects to these potential risks and close monitoring 
will ensure prompt response to any adverse effects with appropriate treatment and/or 
study discontinuation, as indicated.   
Additional risks are minimal and involve the completion of questionnaires, interviews 
and paper-pencil/computerized tests. Some of the questions may be distressing to the 
individual and subjects will be told that they may refuse to answer any questions that they 
so choose. The testing procedure can sometimes cause fatigue but we will ensure plenty 
of resting periods during the session and will instruct subjects to notify staff if they would 
like an additional break. Pain and bruising may be associated with the blood draw for 
screening labs; however, a trained phlebotomist will perform the procedure to avoid any 
additional discomfort. 
7) Provisions for Research Related Injury 
In accordance with Federal Regulations, if anyone is injured from being in the study, they 
will receive medical care and treatment as needed from the Mount Sinai Medical Center.  
However, participants are responsible for the costs of such medical treatment, directly or 
through their medical insurance and/or other forms of medical coverage.  No money shall 
be given to them. 
 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
11 
Revised  9/2/14 
8) Potential Benefits to Subjects 
There may be no immediate potential benefit to the subject from participation in this 
research study; however, the results may provide the bases for larger scale, pivotal trials 
designed to move toward new indications for the study agent and therefore, lead to novel 
options for treating these disabling symptoms. Moreover, although there is no guarantee, 
it is possible that subjects taking isradipine may experience some improvement in 
cognitive deficits associated with SZ. 
 
9) Provisions to Protect the Privacy Interests of Subjects 
Subjects are free to refuse to answer any of the questions that are asked of them in the 
study. If the withheld information is critical to study eligibility the patient may not be 
enrolled.  While enrolled in the study, all tests and procedures will be done in a research 
office at ISMMS ensuring privacy. All research staff will be open to answering any 
questions and will address any concerns of the subjects throughout the duration of the 
study. 
 
10) 
Economic Impact on Subjects 
There is no cost to participants for participating in the study. 
 
11) 
Payment to Subjects 
Subjects will be informed during the informed consent process of the study 
compensation. 
 
 
 
 
12) 
Consent Process 
A potential subject will be approached by a member of the study team after she/he has 
been given permission to do so by the patient’s clinician. The research team member will 
explain the study objectives, procedures, risks and benefits, and answer all questions the 
potential subject may have. Subjects are advised that they can withdraw at any time 
during the study. Subjects will receive a copy of the consent form for the study. Informed 
consent will be documented when the subject signs the consent form that has been 
approved by ISMMS PPHS. 
 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
12 
Revised  9/2/14 
13) 
Process to Document Consent in Writing 
All participants must provide written informed consent.  The consent form will be 
documented in writing.  The consent form has been derived from the standard PPHS 
consent template.   
 
14) 
Vulnerable Populations 
The following vulnerable population types will be excluded from the study: adults unable 
to consent, individuals who are not yet adults, wards of the state, pregnant women, and 
prisoners. 
 
15) 
Multi-Site Human Research (Coordinating Center) 
N/A 
16) 
Community-Based Participatory Research 
N/A 
 
17) 
Sharing of Results with Subjects 
If any preliminary results arise from this study or any related studies are published that 
change the risks associated with this protocol, we will notify all subjects who have 
participated.  Otherwise, results from the analyses will be published in peer-reviewed 
journal articles but will not be transmitted directly to the subjects involved in the 
research. 
 
18) 
IRB Review History 
 
N/A 
 
19) 
Control of Drugs, Biologics, or Devices 
Note: The IDS has its own forms that must be completed and a review process 
that must be followed before the IDS representative will sign off on Appendix B 
for submission to the PPHS. 
The study drug will be stored in secure, temperature-controlled offices on the 
  
 
 
Street within the Laboratory of Neurocognition under the supervision of the 
PI. The principal investigator will be authorizing the study physician to handle and 
control the study drug. 


 
Protocol Title: 
A Molecular Approach to Treat Cognition in Schizophrenia: 
Ca2+ Channel Blockade 
Principal Investigator 
Name/Contact Info:  
Katherine Burdick, PhD 
katherine.burdick@mssm.edu 
Primary Contact 
Name/Contact Info 
Megan Shanahan 
 
Date Revised: 
May 16, 2017 
Study Number: 
HSM# 12-0031, GCO# 12-0679, GCO# 13-1987 
 
13 
Revised  9/2/14