Vanderbilt University Medical Center Press F1 while in any field for context-sensitive help G e n e r a l C l i n i c a l R e s e a r c h C e n t e r E l e c t r o n i c P r o t o c o l A p p l i c a t i o n

Doubleclick to see P. For more information see the GCRC Web site at - http://www.mc.vanderbilt.edu/gcrc/ Review Process

Office use only (P. No.) Protocol Short Title (54 characters max.): Date submitted: (m/d/yy) *Enter short title if full title > 54 characters

Protocol Full Title: *Enter full protocol title here ( title must match IRB study title ) l o c

o Visit Location: GCRC Pediatric CRC t o

r Single-Center Study Multi-Center Study Clinical Study Phase: *Select from list

P Total number of patients in study? Total at Vanderbilt? Duration of study (years): Is this a rare disease study with a TDN (Therapeutic Development Network)? *Select from list Proposed Study Subject Category: *Select from list IRB Status: *Select from list IRB #: IRB Approval Date:

Principal Investigator Name: Degree: *Select from list Title and Department: Phone #: Email: Pager #:

Primary Contact Person If Other Than PI: Phone #: Email: Pager #:

Study Coordinator: s

r Phone #: Email: Pager #: o t

a Co-Investigators: g i First Name, Last Name, Degree Phone Number (a) Department t

s e

v *Enter Co-Investigator #2 full name CI-2 phone # CI-2 Department n I *Enter Co-Investigator #3 full name CI-3 phone # CI-3 Department

*Enter Co-Investigator #4 full name CI-4 phone # CI-4 Department

*Enter Co-Investigator #5 full name CI-5 phone # CI-5 Department

*Enter Co-Investigator #6 full name CI-6 phone # CI-6 Department

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V0.04.23.2007 Submit using e-mail attachment to [email protected] Page 2 Vanderbilt University Medical Center Press F1 while in any field for context-sensitive help If you have submitted your IRB application and your Protocol to the IRB, you do not need to complete # 1- 9. We will obtain your submission from the IRB. If you have submitted an exempt IRB application or if you have not submitted an IRB application, then complete this application. 1. Statement of the Problem this Study Will Address * Type here 2. Hypothesis and Specific Aims * Type here 3. Background and Significance * Type here 4. Preliminary Studies; Progress Reports * Type here 5. Research Design and Methods Answer the question: “What will be done in order to accomplish the specific aims or test the hypothesis”? a) List of procedures and time-table. * Type here b) Data expected, analysis and interpretation * Type here c) Problems and solutions if appropriate * Type here

6. Human Subjects Research Considerations a) Risks and potential risks to Study Subjects: * Type here b) Source(s) of Research Material(s): * Type here c) Adequacy of Protection Against Risks: * Type here d) Describe Recruitment Plan and enrollment process: * Type here e) Describe inclusion / exclusion criteria * Type here

7. Statement Regarding Exclusion of Specific Subject Categories: If applicable, justify exclusion of specific subject categories (gender, ethnicity, children, elderly): * Type here 8. Data and Safety - Monitoring Plan* *As per NCRR requirements, ALL protocols submitted to the GCRC must have a data and safety-monitoring plan. The minimal requirements for a DSMP according to the NCRR Advisory Council include: 1) Adverse event (AE) grading and attribution scale; 2) Plan for unanticipated AE reporting; 3) Plan for annual reporting of AEs; and 4) Plan for safety review (by whom and at what frequency). The level of detail on the DSMP should be commensurate with the level of risk entailed in the study. If you have any questions concerning what information is required, please contact the GCRC Research Subject Advocate (Vikki Thurman). If you are unsure whether your study might need a DSM Board please contact Ms. Thurman. In situations where it is unclear whether a study requires a DSMB or not, the ultimate decision is made by the GAC.

A. Do you have a DSM Board? Yes No

V0.04.23.2007 Submit using e-mail attachment to [email protected] Page 3 Vanderbilt University Medical Center Press F1 while in any field for context-sensitive help B. Summarize the DSMP For This Protocol: * Type here

9. References/Literature Cited * Type here 10. Sample Size Justification and Statistical Analysis Plan: (The GCRC Scientific Advisory Committee will not approve studies that lack a sample size justification or a statistical analysis plan) * Type here 11. Targeted/Planned Enrollment: Enter Number of Subjects in the Table Below Sex/Gender Ethnic Category Females Males Total Hispanic or Latino 0 0 0 Not Hispanic or Latino 0 0 0 Ethnic Category Total of All Subjects 0 0 0

Racial Categories Females Males Total American Indian/Alaska Native 0 0 0 Asian 0 0 0 Native Hawaiian or Other Pacific Islander 0 0 0 Black or African American 0 0 0 White 0 0 0 Racial Categories: Total of All Subjects* 0 0 0 *The “Ethnic Category Total” of All Subjects must be equal to the “Racial Categories Total” of All Subjects. 12. Funding Sources Other Than GCRC Requested Support Describe Funding for this Protocol (Departmental/VUMC, NIH, Other Federal Agencies, Industry, Foundation, or other support). • A copy of the study funding budget is required with this application. • For industry sponsored trials, a copy of the clinical trial agreement is required with application. Send sponsor budget or grant and clinical trial agreement to: [email protected]

* Type here

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Summary of Requested GCRC Services

13. Space, Nursing and Nutritional Services:

Identify projected needs for GCRC space, nursing and nutritional services in the tables below. Note that total number of patients in the two tables should agree with the gender/minority tables on the previous page and also with numbers in your main protocol description.

Inpatient Information Required Nursing Number of Avg No. Of Diet Needs Year Hospital Days Care Inpatients per Inpatient   Year 1 0 0 Year 2 0 0 Year 3 0 0 Year 4 0 0 Year 5 0 0 Total 0

Outpatient Information Avg Hours per Number of Avg No. Of Diet Needs Year Visits per Outpatient Visit Outpatients Outpatient   Year 1 0 0 Year 2 0 0 Year 3 0 0 Year 4 0 0 Year 5 0 0 Total 0  Nursing care Codes: C=Complete, P=Partial, S=Self Care, A=Constant Attendants, V=VCH.  Diet Codes: R=Regular Diet, S=Special Diet. GCRC Nursing Needs * Enter additional GCRC nurse needs here

* Do you need nursing support at Pediatric CRC? Yes No

Special Diet Needs * Enter additional special diet needs here

GCRC Medical Supply Needs * Enter special medical supply needs here

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Sleep Core Section A: Sleep Study Number * Please contact Dr. Beth Malow with questions at: [email protected],, (615) 322-0283

Sleep research studies are a shared resource and there may be scheduling constrains. Overnight studies are generally performed Monday, Tuesday, Wednesday, and Thursday evenings. Other studies (multiple sleep latency tests, hospital wireless) are scheduled around the overnight studies in a way that maximizes access for users. We will make every effort to meet your scheduling needs within our constraints.

Describe briefly the flow of sleep studies for a participant. (Example: Participant undergoes two consecutive nights of PSG with a multiple sleep latency test after the second night. If at least one of the nights is positive for sleep apnea, participant will return for a CPAP trial). * Type here

Total number of participants in Year 1: 0 Total number of requested overnight PSGs (baseline PSGs, CPAP studies) in Year 1: 0 Do these PSGs include a full head EEG? Yes No Do these PSGs include continuous BP monitoring? Yes No Other studies requested (list total number requested in Year 1 next to each study type) Multiple Sleep Latency Test: 0 Hospital Wireless studies: 0 Section B: Scheduling

List your preferences for nights of PSG and other studies. (Example: Preference #1: Participant will undergo a Monday and Tuesday PSG with a multiple sleep latency test on Wed. Preference #2: Participant will undergo a Tuesday and Wednesday PSG with a multiple sleep latency test on Thurs). As stated above, because this is a shared resource, we have constraints on scheduling but will make every effort to accommodate users.

Preference #1: * Type here

Preference #2: * Type here

Section C: Grant Support Please check one of the following

I currently have grant support that can be used to offset the cost of the GCRC Sleep Core. I do not currently have grant support that can be used to offset the cost of the GCRC Sleep Core, but plan to use my pilot data to obtain grant support to offset the cost of the GCRC Sleep Core. Section D:

Additional Needs (e.g., Actigraphy, Specialized Sleep Scoring, Measurement of CPAP compliance) Please describe any additional needs for your protocol * Type here

V0.04.23.2007 Submit using e-mail attachment to [email protected] Page 7 Vanderbilt University Medical Center Press F1 while in any field for context-sensitive help 14. GCRC Core Laboratory Tests and Analyses *Contact Dr. Tom Davis with questions at: [email protected], (615) 322-3011. Biochemical # Tests/ Total Tests Test i) Test Types Subject Requested Catecholamine Serum Urine Whole Blood Plasma 0 0 Catecholamine Serum Urine Whole Blood Plasma 0 0 Nitrogen Serum Urine Whole Blood Plasma 0 0 Basic Metabolic Panel1 Serum Urine Whole Blood Plasma 0 0 Comprehensive Metabolic Panel2 Serum Urine Whole Blood Plasma 0 0 Hepatic Function Panel3 Serum Urine Whole Blood Plasma 0 0 Renal Function Panel4 Serum Urine Whole Blood Plasma 0 0 Urea/BUN Serum Urine Whole Blood Plasma 0 0 Creatinine Serum Urine Whole Blood Plasma 0 0 Sodium Serum Urine Whole Blood Plasma 0 0 Potassium Serum Urine Whole Blood Plasma 0 0 Chloride Serum Urine Whole Blood Plasma 0 0

CO2 Serum Urine Whole Blood Plasma 0 0 Glucose Serum Urine Whole Blood Plasma 0 0 Calcium Serum Urine Whole Blood Plasma 0 0 Magnesium Serum Urine Whole Blood Plasma 0 0 Aliquot Serum Urine Whole Blood Plasma 0 0 Total Protein Serum Urine Whole Blood Plasma 0 0 Albumin Serum Urine Whole Blood Plasma 0 0 SGOT (AST) Serum Urine Whole Blood Plasma 0 0 SGPT (ALT) Serum Urine Whole Blood Plasma 0 0 GGT Serum Urine Whole Blood Plasma 0 0 LDH Serum Urine Whole Blood Plasma 0 0 Alkaline Phosphatase Serum Urine Whole Blood Plasma 0 0 Total Bilirubin Serum Urine Whole Blood Plasma 0 0 Direct Bilirubin Serum Urine Whole Blood Plasma 0 0 Phosphorus Serum Urine Whole Blood Plasma 0 0 Total Cholesterol Serum Urine Whole Blood Plasma 0 0 Triglycerides Serum Urine Whole Blood Plasma 0 0 Melatonin Serum Saliva Whole Blood Plasma 0 0 6-Sulfatoxymelatonin Serum Urine Whole Blood Plasma 0 0 Cortisol Serum Saliva Whole Blood Plasma 0 0 Nt-pro BNP Serum Urine Whole Blood Plasma 0 0 Pregnancy Test Serum Urine Whole Blood Plasma 0 0

1 Basic Metabolic Panel: Crea, Na, K, Bun, Glu, Ca, Cl, CO2 2 Comprehensive Metabolic Panel: BMP, TP, Alb, AST, ALT, TBIL, Alk Phos 3 Hepatic Function Panel: DBIL, TBIL, Alk Phos, TP, AST, ALT, Alb 4 Renal Function Panel: BMP, Alb, PO4

 These tests are to be ordered for research purposes only. They cannot be used for diagnostic or treatment purposes.  Tests are assayed on a Routine Basis Monday through Friday.

V0.04.23.2007 Submit using e-mail attachment to [email protected] Page 8 Vanderbilt University Medical Center Press F1 while in any field for context-sensitive help 15. Requested GCRC Support for Hospital Ancillary Services * COST/TEST ARE ESTIMATES AND SUBJECT TO CHANGE. USE ONLY FOR GCRC PROTOCOL SUBMISSION PURPOSES. Total Tests Total *Estimated # Tests / For Entire Amount Name of Test or Procedure Cost / Test Subject Study Requested Aldosterone $80.00 0 0 $0.00 Basic Met Panel ** $36.00 0 0 $0.00 CBC (Hemogram) $17.00 0 0 $0.00 CBC, Diff, Plts. $27.00 0 0 $0.00 s

t Cholesterol $39.00 0 0 $0.00 s

e Comp Met Panel ** $40.00 0 0 $0.00 T

CRP $7.00 0 0 $0.00 t

n CSF Culture $35.00 0 0 $0.00 e

i CSF Cytology $34.00 0 0 $0.00 t

a CSF Glucose $13.00 0 0 $0.00 p CSF Protein $13.00 0 0 $0.00 n I

HGBA1c $15.00 0 0 $0.00 d

r Insulin – Plasma $26.00 0 0 $0.00 a Liver Function Panel ** $37.00 0 0 $0.00 d

n PT $16.00 0 0 $0.00 a

t PTT $24.00 0 0 $0.00 S Renin – Plasma $78.00 0 0 $0.00 Thyroxine – T4 $25.00 0 0 $0.00 Urinalysis w/ microscopy $13.00 0 0 $0.00 F MRI 90 Minutes $675.00 0 0 $0.00 0 .

p *Enter information here $0.00 0 0 $0.00 n I

*Enter information here $0.00 0 0 $0.00 r

e *Enter information here $0.00 0 0 $0.00 h t

O *Enter information here $0.00 0 0 $0.00 0 Aldosterone $80.00 0 0 $0.00 Basic Met Panel ** $36.00 0 0 $0.00 CBC (Hemogram) $17.00 0 0 $0.00

s CBC, Diff, Plts $27.00 0 0 $0.00 t

s Cholesterol ** $39.00 0 0 $0.00

e Comp Met Panel ** $40.00 0 0 $0.00 T

t CRP $7.00 0 0 $0.00

n CSF Culture $35.00 0 0 $0.00 e i

t CSF Cytology $34.00 0 0 $0.00 a CSF Glucose $13.00 0 0 $0.00 p t CSF Protein $13.00 0 0 $0.00 u

O HGB A1c $15.00 0 0 $0.00

d Insulin – Plasma $26.00 0 0 $0.00 r

a Liver Function Panel ** $37.00 0 0 $0.00 d PT $16.00 0 0 $0.00 n

a PTT $24.00 0 0 $0.00 t

S Renin - plasma $78.00 0 0 $0.00 Thyroxine – T4 $25.00 0 0 $0.00 Urinalysis w/ microscopy $13.00 0 0 $0.00 fMRI 90 minutes $675.00 0 0 $0.00 0 r

e *Enter information here $0.00 0 0 $0.00 h t *Enter information here $0.00 0 0 $0.00 O .

p *Enter information here $0.00 0 0 $0.00 t 0 u

O a. Total Amount Requested from GCRC for Ancillaries $0.00 b.

** These tests are available in the GCRC Core Lab. If you are requesting these tests from the hospital lab, provide a scientific justification.

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16. Drug and Investigational Pharmacy Support (check only items that apply) *Contact Hope Campbell with questions and fee quotes at: [email protected], (615) 343-6537.

Requesting GCRC pay for any drugs used in this study? *If checked, describe drugs, amounts, and costs

Requesting GCRC pay for the Investigational Pharmacy costs? *If checked, describe services and costs

Drug Cost $0.00 $0.00 $0.00 $0.00 1) Pharmacy Fees Initiation Fee $0.00 Dispensing Fee $0.00 Other: $0.00

17. Biophysical Total Estimated # Tests/ Total Tests Amount Test Cost / Test Subject Requested Requested Body Composition – Bod Pod $40.00 0 0 $0.00 Body Composition – DEXA $156.00 0 0 $0.00 Body Composition – $0.00 0 0 $0.00 Bioelectrical Impedance Body Composition – $0.00 0 0 $0.00 Underwater Weighing Resting Metabolic Rate – $90.00 0 0 $0.00 Metabolic Cart Resting Metabolic Rate – 24 $0.00 0 0 $0.00 Hour EE (Chamber) Test 0 Treadmill Testing –VO2 Max $10.00 0 0 $0.00 Physical Activity $0.00 0 0 $0.00 Monitoring EEG $0.00 0 0 $0.00 Tilt Testing $0.00 0 0 $0.00 EKG without interpretation $0.00 0 0 $0.00 Other: $0.00 0 0 $0.00 Total $0.00

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Genetic Estimated Total Tests Total Amount Test Test Type Cost / Test Requested Requested DNA Extraction Whole Blood (1-5ML) $24.00 0 $0.00 DNA Whole Blood (10ML) $29.00 0 $0.00 DNA Buccal $24.00 0 $0.00 Total $0.00

A. Genotyping I. Type of Genotyping Studies Requested: Replace this text with your own. II. Rationale for Requested Genotyping Studies (including pertinent preliminary data): Replace this text with your own. III. Cost of Genotyping: Contact Cara Sutcliffe at 936-2744 for the cost of your sample analysis and provide the cost of your analysis in the table below.

Total Number Cost Genotyping Genotypes 0 $0.00 0 $0.00 0 $0.00 0 $0.00 2) Total Number of Genotypes 0 $0.00

19. Mass Spectrometry Test Test Type Total Samples Cost Mass Spectrometry Serum Urine Plasma 0 $0.00 Protein Profiling Serum Urine Plasma 0 $0.00 Please contact Dr. David Hachey at 3-8382 or e-mail ([email protected]) prior to protocol submission to discuss needs and obtain a cost estimate of the time needed to run project samples.

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Immunology Core # Tests Total Tests *Assay Per Total Cost Class Requested Cost Subject T Cell Subsetting 0 CD3+ 0 0 $15.00 $0.00 CD4+ 0 0 $15.00 $0.00 CD8+ 0 0 $15.00 $0.00 Other (specify in paragraph below) 0 0 $0.00 $0.00 CD34 Enumeration 0 0 $70.00 $0.00 Cytokine Beads Array 0 Inflammation Cytokines 0 0 $60.00 $0.00 (IL-8, IL-1, IL-6, IL-10, TNF, and IL-12p70) Apoptosis 0 0 $55.00 $0.00 (Human PARP, Bcl-2 and Caspase 3) Anaphylatoxin (C4a, C3a and C5a) 0 0 $45.00 $0.00 Chemokine (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, 0 0 $56.00 $0.00 CCL2/MCP-1, and CXCL10/IP-10) Th1/Thy2 cytokines II 0 0 $60.00 $0.00 (IL-2, IL-4, IL-6, IL-10, TNF, and IFN-g) Th1/Th2 cytokines 0 0 $60.00 $0.00 (IL-2, IL-4, IL-5, IL-10, TNF, and IFN-g) Single/Combo (Multiplex.) Array Cytokine Flex Set IFN-γ,G-CSF, Fas-Ligand, Eotaxin, Angiogenin, Basic FGF, GM-CSF, TNF, IL- 1beta, RANTES, IL-3, IL-4, IL-6, IL-7, IL-8, IL- 0 0 $10.00 $0.00 9, IL-10, IL-12p70, IP-10, LT-a, MIG, MCP-1, MIP-1beta, VEGF. Phospho Flex Set BTK (Y551), eNOS (S1177), ERK1/2 (T202/Y204), ITK (Y511), JNK1/2 (T183/Y185), p38 (T180/Y182), PCLγ (Y783), 0 0 $10.00 $0.00 RSK (T573), SYK (Y352), STAT-1 (Y701), ZAP-70 (T319). Enzyme-Linked ImmunoSorbent Assay (ELISA) C-Reactive Protein (hsCRP) 0 0 $8.00 $0.00 ELISPOT 0 IFN-g 0 0 * $0.00 $0.00 Intracellular cytokine staining 0 IFN-g 0 0 * $0.00 $0.00 Total Request $0.00

* The prices listed are for GCRC approved protocols. The price is designed to cover reagent costs. Labor is provided by the GCRC support grant.

The GCRC Advisory committee may approve up to $9000 in assay expenses without charge to investigators.

* All requests for human immunology core services require prior consultation. Please contact Dr. Jim Crowe with consultation questions at [email protected] Please contact Kevin Weller at 3-9935 with technical questions.

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Bionutrition Support Required (check all items that apply) *Contact Dr. Maciej Buchowski with questions at: [email protected], (615) 343-4192. Diet instruction or nutrition education Nutrient intake analysis (e.g.,diet records, 24 hr recall, food frequency questionnaire, weighed meals, etc.) Nutrient controlled diet Growth assessment: (e.g., skinfold, circumference, segment measures, etc.) Daily energy balance assessment Daily nutrient balance assessment Other? *Enter other bionutrition needs, otherwise leave blank

Biostatistical Support Required (check all items that apply) *Contact Dan Byrne with questions at: [email protected], (615) 322-4228. Protocol Review Study design consultation Sample size estimation Statistical analysis consultation Software tool selection/training Manuscript review Primary Biostatistician for this study: *Name/phone/email

Research Subject Advocate (check all items that apply) *Contact Vicky Thurman with questions at: [email protected] (615) 343-6452. Protocol Review Human subject risks, study alternatives, protections and mitigation support DSMP/DSMB planning support Serious Adverse Event (SAE) definitions; procedures assistance HIPAA compliance Other *Enter other RSA needs, otherwise leave blank

Informatics (check all items that apply) *Contact Dr. Paul Harris with questions at: [email protected], (615) 322-6688. Protocol Review Web-Based Research Database (REDCap) Research volunteer subject recruitment registry Measurements and analysis methods and development Poster printing and use of shared computing environment t

n As Principal Investigator, I agree: e 1. That all information in this application is complete and true to the best of my knowledge. m 2. That all key personnel on this protocol are IRB-certified. e

e 3. That I will provide all information requested by the GCRC in a timely manner. r

g 4. That I will inform the Program Director and Research Safety Advocate of any adverse events. A 5. That I will credit the GCRC NIH grant M01 #RR00095 in any subsequent published literature.

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