Diuretic/Cool Dialysate Trial
Phase: NA
Conditions: Chronic Kidney Insufficiency
Sponsor: University of New Mexico

DIDIT: Diuretic/Cool Dialysate Trial
   
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PROTOCOL TITLE:
DIDIT: Diuretic/Cool Dialysate Trial
PRINCIPAL INVESTIGATOR:
Mark L. Unruh, MD
Internal Medicine; Nephrology
VERSION NUMBER:
V7.0
DATE:
July 12th, 2019
REGULATORY FRAMEWORK:
Please indicate all that apply:
DOD (Department of Defense)
DOE (Department of Energy)
DOJ (Department of Justice)
ED (Department of Education)
EPA (Environmental Protection Agency)
FDA (Food and Drug Administration)
HHS (Department of Health and Human Services)
Other:      
Is this a clinical trial under ICH-GCP E6?   
 Yes   
 No
If yes, please confirm that the research team is familiar with and agrees to comply with 
the investigator requirements cited in ICH-GCP E6.  
 Yes   
 No 
ICH-GCP E6 can be accessed by copying and pasting this URL into your browser: 
http://www.fda.gov/downloads/Drugs/Guidances/ucm073122.pdf

DIDIT: Diuretic/Cool Dialysate Trial
   
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Table of Contents
1.
Objectives.....................................................................................................................3
2.
Background ..................................................................................................................3
3.
Study Design ................................................................................................................4
4.
Inclusion and Exclusion Criteria ..................................................................................5
5.
Number of Subjects......................................................................................................7
6.
Study Timelines............................................................................................................7
7.
Study Endpoints ...........................................................................................................8
8.
Research Setting...........................................................................................................8
9.
Resources Available.....................................................................................................8
10.
Prior Approvals.........................................................................................................9
11.
Multi-Site Research ..................................................................................................9
12.
Study Procedures ......................................................................................................9
13.
Data Analysis..........................................................................................................11
14.
Provisions to Monitor the Data to Ensure the Safety of Subjects...........................12
15.
Withdrawal of Subjects...........................................................................................12
16.
Data Management/Confidentiality..........................................................................13
17.
Data and Specimen Banking...................................................................................14
18.
Risks to Subjects.....................................................................................................14
19.
Potential Benefits to Subjects .................................................................................15
20.
Recruitment Methods..............................................................................................15
21.
Provisions to Protect the Privacy Interests of Subjects ..........................................15
22.
Economic Burden to Subjects.................................................................................16
23.
Compensation .........................................................................................................16
24.
Compensation for Research-Related Injury............................................................17
25.
Consent Process......................................................................................................17
26.
Documentation of Consent .....................................................................................18
27.
Study Test Results/Incidental Findings ..................................................................18
28.
Sharing Study Progress or Results with Subjects...................................................18
29.
Inclusion of Vulnerable Populations ......................................................................18
30.
Community-Based Participatory Research.............................................................18
31.
Research Involving American Indian/Native Populations .....................................19
32.
Transnational Research...........................................................................................19
33.
Drugs or Devices ....................................................................................................18
Checklist Section ...............................................................................................................18

DIDIT: Diuretic/Cool Dialysate Trial
   
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1. Objectives
Each year in the United States, approximately 100,000 people start maintenance dialysis 
therapy suffering high mortality rates, frequent hospitalizations, and marked decline in 
quality of life. The overarching aim of the “Diuretic/Cool Dialysate Trial” (DIDIT) is to 
improve outcomes of incident hemodialysis (HD) patients by recognizing the importance of 
residual renal function (RRF). This pilot study will demonstrate the feasibility of loop 
diuretic (bumetanide) use and/or cool dialysate, and will obtain preliminary information that 
will inform future examination into whether these interventions will slow the rate of RRF 
decline in HD, improve quality of life, and reduce overall mortality.  
The proposed pilot study challenges the current widespread paradigm of discontinuing loop 
diuretics when initiating chronic HD and/or maintaining the dialysate at a constant 
temperature of 37 °C for all patients.
Specific Aim: We aim to conduct a pilot randomized controlled trial (RCT) to assess 
feasibility and safety, and to inform the design of a full-scale trial of bumetanide and/or cool 
dialysate using a two-by-two factorial design, compared to usual care.
The long-term goals of this proposed work are to optimize survival, health-related quality of 
life (HRQOL) and other outcomes of HD patients by providing them a low dose of a loop 
diuretic and by lowering the dialysate temperature at the start of their transition to dialysis 
therapy. The design will permit a rapid scaling-up of the interventions to a larger clinical trial 
since the incremental dialysis prescription takes advantage of resources and personnel that 
are readily available. This pilot study will substantially accelerate our ability to address 
fundamental issues in the care of this population, which is burdened by low HRQOL and can 
change the current paradigm and practice pattern.
Hypothesis: Use of bumetanide and/or cool dialysate during the first six months of HD will 
slow the rate of RRF decline, decrease inflammation and oxidative stress, improve HRQOL 
and decrease mortality. To explore this hypothesis we propose to conduct a pilot RCT. 
2. Background
Many clinical trials have examined the extent to which outcomes could be improved in the 
prevalent dialysis population. However, incident HD patients have been largely overlooked 
despite their high mortality, morbidity and marked decrements in HRQOL. This proposal 
addresses the gap of care in incident HD patients by focusing on maintaining RRF, one of the 
strongest predictors of survival and HRQOL in the first year of dialysis therapy.
Many different factors have been implicated in the decline of RRF in HD, and therefore 
many different therapeutic strategies have been suggested for the preservation of RRF in 
these patients. In this study, we intend to evaluate two different therapeutic approaches: the 
use of a loop diuretic (bumetanide) and/or the use of cool dialysate during the HD session. 

DIDIT: Diuretic/Cool Dialysate Trial
   
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Diuretic therapy remains the cornerstone of managing fluid overload. The role of diuretics in 
managing HD patients is not yet clearly defined (1). Diuretics can be used to minimize RRF 
loss in chronic HD patients (1). More specific loop diuretics are not nephrotoxic, confer 
better fluid balance, maximize urine production, allow less aggressive ultrafiltration and are 
associated with decreased cardiac mortality (1, 2). The DOPPS study verified that loop 
diuretics are the most often prescribed diuretics to chronic HD patients (2). In clinical 
practice, many patients begin HD chronically using small doses of a loop diuretic, but since 
there is little evidence that these are beneficial, their use is suspended when the volume of 
residual diuresis is reduced to minimum values.
While currently not the standard of care in the US, cool dialysate may confer significant 
survival benefits. Cool dialysate has been associated with decreased intradialytic hypotension 
which may minimize kidney injury and slow RRF decline. The current US paradigm is to 
maintain dialysate temperature according to physician’s discretion, usually at 37 °C. Cool 
dialysate may decrease inflammatory and oxidative stress from HD therapy, and thus 
minimize kidney injury, slow the decline of RRF, and decrease morbidity and mortality. This 
important strategy of preserving RRF is not routinely applied to HD patients.
The use of bumetanide is also not currently the standard of care, but additionally may provide 
survival benefits by minimizing RRF loss. Specifically, bumetanide is not nephrotoxic, 
confers better fluid balance, maximizes urine production, may allow less aggressive 
ultrafiltration and is associated with decreased cardiac mortality. 
Each year in the US approximately 100,000 people begin chronic dialysis and 80,000 die 
resulting in the growth of the prevalent population which now exceeds 400,000 patients on 
chronic dialysis. Prevalent HD patients have a mortality rate of 20% per year. Even more 
disconcerting is that during the first six months of therapy the annualized mortality is 35-
40%. Although many clinical trials have examined the extent to which outcomes could be 
improved in the prevalent dialysis population, incident HD patients have been largely 
overlooked despite their high mortality, morbidity and marked decrements in HRQOL. This 
proposal addresses the crisis of care in incident HD patients by focusing on maintaining 
RRF, one of the strongest predictors of survival and HRQOL in the first year of dialysis 
therapy.
3. Study Design
This pilot RCT will demonstrate the feasibility and safety of performing a large scale study 
of diuretic use and/or cool dialysate by examining recruitment, retention, and key outcomes. 
This study will further assess whether the use of a diuretic compared to non-use of a diuretic 
(placebo) and/or the use of cool dialysate (35.5 ºC) compared to 37 ºC for up to 6 months 
will improve RRF, improve HRQOL and reduce hospitalizations. by randomizing 20 chronic 
hemodialysis patients  from DCI centers in the greater Albuquerque area, to either 
bumetanide and cool dialysate randomized in a two-by-two factorial distribution. 

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The study sample will be selected using an approach to limit drop-out while enhancing 
generalizability and the main analysis will be intention-to-treat. Considering the intervention 
cannot be double-blinded, we have made efforts to reduce bias by using objective outcomes 
and blinding the assessment of patient-reported outcomes. Subjects will be recruited for 18 
months. An additional 6 month period will be used to complete the intervention in the last 
subjects and they will be re-assessed at month 8 for an end of study evaluation. The 
recruitment and participation parameters for development of this formal RCT will assess 
whether the large scale study can meet enrollment criteria and target timelines, and whether 
patients can be maintained on the study protocol without safety concerns.
In this pilot study we will assess as primary patient outcomes: 

The change in RRF over 6 months

The association of cool dialysis and/or diuretic with inflammation

The association of cool dialysis and/or diuretic use with acute kidney injury (AKI) 
biomarkers. 
The secondary patient outcomes will be: 

Change in HRQOL

Time to first-hospitalization.
Being a pilot study, our focus is on assessing whether changes in RRF can be detected with 
the proposed technique (urinary creatinine and urea  clearance). Biomarkers of inflammation 
and AKI will be collected to supplement the functional measurement of renal filtration and as 
surrogate biomarkers of benefit or safety (e.g. nephrotoxicity) that can be monitored in the 
large scale study.
4. Inclusion and Exclusion Criteria
Hemodialysis patients required for this pilot project will be identified from the patient 
population treated at DCI centers in the greater Albuquerque area. The average age of 
patients at the study sites is approximately 58 years, and the population is roughly split 
between genders and is racially diverse. Approximately 95% of the dialysis clinic 
population speak or understand English. The study site population demographics are similar 
to those in the Southwestern region and include more Hispanic patients than nationally. NIH 
standards for collecting data will be maintained, and when providing informed consent the 
investigators will rely on two separate questions for patients to self-identify ethnicity and 
race (in that order).
No Diuretic
  (placebo)
      and
37oC dialysate
   No Diuretic
   (placebo)
and
35.5°C dialysate
Diuretic
and
37oC dialysate
Diuretic
and
35.5°C dialysate

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The study is open to all volunteers, irrespective of gender, race, ethnicity, or sexual 
preference. Women will constitute nearly half of the expected sample, and minorities are 
well represented. This is not an NIH-defined Phase III Clinical Trial, but analyses will be 
conducted at the conclusion of the study to determine whether the intervention affected 
women or men or members of minority groups and their subpopulations differently.
       Consented participants must have adequate RRF (See second exclusion bullet below) to    
complete this study. Adequate RRF is determined by the result of the first 24-hour urine 
collection. The participant’s RRF will either allow them to continue or exclude them from 
the study.

Participants with adequate RRF will be randomized to one of the four study arms 
listed above.

The randomization process may take up to 7 days.

Randomized participants will have any ordered diuretics discontinued before they 
begin taking the “study drug”

There is no “taper” or “time delay for stopping their diuretic and starting the “study 
drug” 
Inclusion Criteria:

Age ≥18 years

Primary speaking language is English or Spanish.

Patient is on chronic in-center HD prior to randomization

HD takes place at one of the participating Dialysis Clinic Inc. (DCI) sites during the 
data collection period.

Subject urinates more than 200 ml of urine  a day (self-reported).

Patients must be willing and able to sign the consent form. 
Exclusion Criteria:

Age <18 years of age. 

RRF <2 mL/min/1.73 m2 as determined by 24-hour urine collection.

Allergy or contraindication to bumetanide.

Expectation that native kidneys will recover.

History of poor adherence to treatment.

Unable to verbally communicate. 

Requires more than 3 HD treatments per week due to medical co-morbidity (such as, 
but not limited to: severe volume overload requiring frequent HD e.g. in systemic 
oxalosis, or requiring total parenteral nutrition).

Scheduled for living donor kidney transplant in the next 6 months.

Intention to change to peritoneal dialysis, or home HD in the next 6 months.

Plan to relocate to another center within the next 7-8 months.

Expected geographic unavailability at a participating HD unit for >2 consecutive 
weeks or >4 weeks total during the next 6 months (excluding unavailability due to 
hospitalizations)

Post kidney transplantation

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
Currently in an acute or chronic care hospital

Life expectancy <6 months or intention to withdraw dialysis therapy within 6 months.

Current pregnancy, nursing mother or actively planning to become pregnant in the 
next 8 months 

Current use of investigational drugs 

Participation in another non-observational clinical trial that contradicts or interferes 
with the therapies or measured outcomes in this trial

Unable or unwilling to follow the study protocol for any reason (including mental 
incompetence)

Unable or unwilling to provide informed consent or sign IRB-approved consent form.
The following special populations will not be included in this study:

Patients who are too infirm or lack the capacity to meaningfully participate in 
medical decisions and to sign the informed consent form.

Children and adolescents constitute <2% of the dialysis population, and our 
preliminary survey of the study sites found no children and adolescents were active 
patients. In any case, the renal and other physical factors of children and adolescents 
with ESRD are not directly comparable to those of adults.

Prisoners.
The study is open to all volunteers, regardless of gender, race, ethnicity, or sexual 
preference. All study consents and documents will be in English or Spanish, except for the 
PROMIS-57, which is currently unavailable in Spanish. Patients who are Spanish speaking 
only will not complete this questionnaire. If the questionnaire becomes available, we will 
add it with IRB approval. 
5. Number of Subjects
Up to 50 patients may be recruited/consented for this study. 
It is unknown, at this time, how many eligible subjects will need to be approached in 
order to attain the desired number of study participants. We will continue to recruit until 
20 patients have been followed to completion post protocol modification. 
6. Study Timelines

The duration of an individual subject’s participation in this research is 8 months.

Subject recruitment will occur over 18 months. 

See table 1 “Schedule of study tests/assessments/intervention”, Study Procedures 
section 12, for procedure timeline.

Anticipated data collection is to be completed by the end of year 2. Once all data has 
been collected and verified, data analysis and report preparation will take place over a 
6 month period.
7. Study Endpoints

DIDIT: Diuretic/Cool Dialysate Trial
   
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
Recruit and randomize 25 incident chronic in-center  HD patients  with urine output 
>200 mL/day and  to 3 mg of oral bumetanide once daily and/or to cool dialysate 
(35.5 ºC).

Estimate recruitment and retention rates anticipated in a full-scale study.

Compare changes in RRF markers between groups.

Collect preliminary data on adverse events (AE) and serious adverse events (SAE), 
biomarkers of inflammation and injury to native kidneys, HRQOL, health care 
utilization and other potential outcomes of a full-scale trial.
8. Research Setting
Potential subjects will be recruited at Dialysis Clinic Inc. (DCI) centers located in 
Albuquerque and Rio Rancho. 
Pre-dialysis and 24 hour urine collections will take place at the participant’s home. As 
appropriate to the study timeline, lab values will be collected from the participant’s DCI 
records.
Study blood samples collected at DCI will have their initial spin done at DCI by study 
personnel using DCI’s centrifuge. These samples and any collected urine samples will be 
transported to a UNM study lab or to a Tricore® lab for final processing.  No collected 
specimens will be sent to DCI laboratory.
9. Resources Available
Dr. Mark Unruh, MD is the UNM Nephrologist overseeing this study. This site has been    
granted approval to recruit and complete study visits at the Albuquerque, New Mexico 
Dialysis Clinics Inc. and the Rio Rancho clinic. The PI, sub-investigators, biostatistician, 
micro-RNA specialist, lab staff and study coordinators and research assistants make up 
the study team. This team has broad expertise to successfully complete the proposed aim 
and efficiently deliver findings for immediate clinical and public health application. 
Study physicians will be responsible for medical decision-making,  and for ordering and 
the evaluation of necessary diagnostics and therapeutics for this study. 
The 20 recruited/consented subjects that will complete this study will be recruited at the 
four DCI clinics in Albuquerque and at the Rio Rancho DCI clinic. The four DCI study 
sites should be able to supply the research subjects needed to be recruited for this study. 
Recruitment will last 18 months. An additional 6 month period will be used to complete 
the intervention in the last subjects.
The study investigators recognize that recruitment is the major factor for a successful 
RCT and will use a multi-faceted approach to enhance recruitment. First, the 

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nephrologists and staff of the dialysis units will be informed of the study and will provide 
materials to help explain the importance of study participation. The physicians and 
dialysis staff will also be educated on the study rationale and the scientific importance of 
study participation. The dialysis clinics and nurse educators will be provided with 
brochures and posters that will be conspicuously displayed in the dialysis clinic waiting 
areas. Special attention will be placed on the recruitment of minority participants. 
10.Prior Approvals
The following approvals have been obtained for this study:

Bumetanide drug form attachment

Departmental Scientific Review Form
11.Multi-Site Research
This is not a multi-site study
12.Study Procedures 
 Table 1: Schedule of the study tests/assessments/intervention during the pre-trial (4 wks), 
     
intervention (24 wks or 6 months) and post-trial periods (4 wks).
 
Study Phases 
p
r
e
intervention 
p
o
s
t
Time to do
Measurements/Tests
Month      
0
1
2
3
4
5
6
7
Randomization Intervention: (to one of the following arms)

Cool dialysate and placebo 

Cool Dialysate and Bumetanide (3mg/day)

Isothermic dialysate and placebo 

Isothermic dialysate and Bumetanide (3mg/day)
X
Issue (Bumetanide or placebo): For participants whose pre-intervention 24-
hour urinary Creatinine and Urea clearance results allow them to complete 
the study, any current diuretic will be discontinued prior to taking the “study 
drug”.
X
X
Intervention
Bumetanide/placebo  compliance check
X
X
During 
Dialysis
Routine: (Obtain from DCI monthly labs)

Albumin (g/dL)

Hemoglobin (g/L)

Intact parathyroid hormone (pg/ml)

Kt/V

Potassium (mEq/L)

Calcium (mg/dL)

Sodium (mEq/L)

BUN (mg/dL)

Creatinine (mg/dL) 
X
X
X
X
X
X
X
X
Collect with 
DCI monthly 
labs if values 
are older than 
30 days
Blood tests & HD Rx
Additional blood tests: [Total blood: 11ml: 10ml collected; 1ml waste]

B2-microglobulin (drawn pre- and post-HD) 

Cystatin  

NGAL 

KIM-1 

CRP (mg/L)
X
X
X
Collected with 
DCI monthly 
labs 

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
IL-6

TNF-α

IL-1β
microRNA (drawn pre- and post-HD) [Total blood: 8mls; no waste] 
X
X
Pregnancy testing (blood serum testing)  [1ml]
X
Prior to 
randomization
HD treatment data collected: (From DCI  pt. Chairside flow sheet)

HD Run time 

Membrane type 

Dialysate bath

QB (Blood flow rate: BFR ml/min)

QD (Dialysis fluid flow rate: DFR ml/min)

UF (Ultrafiltration) time 

BP (Every 30 minutes and min & max) 

Pre & Post dialysis weight 

Height (one time only)
X
X
X
X
X
X
X
X

Questionnaire

Dialysis Symptom Index

PROMIS-57
X
X
X
 phone or in 
person (30 
minutes)
Charlson comorbidity index (CCI) and underlying kidney disease
X
X
X
X
3-5 min
Medications: 

In-center 
o
EPO 
o
Iron 
o
Vitamin D 

Outpatient medications
X
X
X
X
X
X
X
X
Demographics: 

Age

Gender

Race

Ethnicity

Marital status 
X
Adverse Events: 

Emergency room visits

Hospitalization(s)

Outpatient visits

Mortality

Transplantation

PD (Peritoneal dialysis)

Transfer to other unit

Relocation 

Hypotensive episode

Dialysis access event
o
Clotting
o
Stenosis
o
Revision
o
New graft or catheter
X
X
X
X
X
X
X
X
Comorbidity & Clinical  data
History and physical exam by MD (PI, sub-I or their designees)
X
Study Staff
24 hour urine collection: RRF 

Start collecting urine day before midweek dialysis session (Note 
date/time)

Stop collecting urine 24 hours later (Note date/time) 
o
Creatinine 
o
Urea
o
X
X
X
Collected 
before a 
midweek 
dialysis 
session 
Urine
*Urine fresh void: [20mls]

Urinary cystatin C

Urine creatinine 

uNGAL
X
X
X
Collected before 
dialysis session 

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
uKIM-1

uHGF

*Urinary microRNA (taken from fresh void)
X
X
13.Data Analysis
For both studies, patient characteristics and outcomes will be summarized by study arm. 
Primary outcomes include 6-month change in RRF. Differences between baseline and 6 
months will be calculated and analyzed with a mixed model that incorporates potentially 
important covariates, such as age, gender and ethnicity. For measurements that will be 
taken monthly, such as albumin, a repeated measures analysis of variance also will be 
conducted on the measurements rather than the differences. If needed, transformations or 
analyses based on ranks will be utilized. This approach will also be used for other 
outcomes that can be treated as continuous variables, such as HRQOL, inflammatory 
markers and the number of days of hospitalization. For discrete variables, such as the 
number of hospitalizations, either logistic regression or Poisson regression will be used. 
The time to first hospitalization will be examined using Kaplan-Meier plots. To adjust 
for study site and baseline covariates, the proportional hazards model will be used. All 
analyses will be intent-to-treat, in that patients will be included in analyses regardless of 
whether the intervention was applied as intended. Estimates of mean change will be 
obtained along with 95% confidence intervals. All analyses will be conducted in SAS. 
This pilot study will inform the design of a larger clinical trial. For Specific Aim 2, the 
proportions recruited and retained will be estimated. With a recruitment and 
randomization of 20 patients, the proportion retained can be estimated to within ± 0.18 
with a 95% confidence interval. Estimates of mean changes, along with estimates of 
variability, will be obtained and used in designing the larger clinical trial.
14.Provisions to Monitor the Data to Ensure the Safety of Subjects
An independent Investigator Monitor will review all data captured for the study including 
unanticipated events. This will allow us to assess whether more frequent monitoring will 
need to take place and how it will affect others currently enrolled. The Investigator 
Monitor will have the authority to recommend stopping the study early or modifying the 
study design for safety concerns. He/she will review  source documents and compare 
them for accuracy against data currently collected. The Investigator Monitor will meet 
with the Principal Investigator to discuss the progress of the patients enrolled in the 
study. The Investigator Monitor will review the progress of the study within 2 weeks 
after the first patient is randomized into the study. The Investigator Monitor and the 
Principal Investigator will conduct monitoring visit approximately every 3 months 
thereafter. The Investigator Monitor will terminate the study if the safety, welfare and 
health of patients is jeapordized due to conducting the study according to protocol. 
Unanticipated events will be reported by the research team to the Investigator Monitor 

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and the IRB within 24 hours of becoming aware of the event. The investigators must 
assess the adverse event (AE)/serious adverse event (SAE) relationship to the 
hemodialysis frequency, the diuretic and/or iohexol. The research team will also be 
responsible for preparing and submitting the reports. Every effort will be made to protect 
subject confidentiality throughout the study. In order to preserve privacy of study data, a 
series of security procedures will be undertaken which are routinely used by UNM. All 
information will be kept confidential, and paper patient data will be maintained in a 
secure location under lock and key. Data collected from study evaluations will be 
identified by study identification codes, and only numeric identifiers will be stored in the 
databases. No data element that alone or in combination can identify specific individuals 
will be entered. Identifying features including names, Social Security Numbers, and 
address may be provided to the PI or research assistant (RA), but will not be available to 
the database or the analyst. Any identifying data will be kept in a secure locked file by 
the PI and RA separate from the study database. Through the use of the security measures 
available with our hardware and software, access to information will be restricted on a 
‘need-to-know’ basis.
15.Withdrawal of Subjects
Subjects may withdraw from this study at any time. Subjects should notify the study PI 
or staff member of their intent to withdraw in writing. Information collected prior to 
withdrawal will remain part of the study.
Active treatment with the study interventions will be terminated if the patient:

Withdraws their informed consent

Is unable to follow/comply with study procedures

Undergoes kidney transplantation

Transfers to home dialysis 

Transfers care to a dialysis facility outside of the Albuquerque DCI 
clinics or Rio Rancho.  

Becomes pregnant while on study drug.
16.Data Management/Confidentiality
For this study, pre-screened eligible patients will be tracked using an ACCESS® 
database which is stored on a secured UNM HSC network drive. The following PHI is 
included in this database: subject’s name and contact number; patient’s emergency 
contact name and phone number; HD start date; age. This database will be used for study 
visit scheduling only. Participant name and other identifying information will be linked to 
a unique study ID once consented.  This study ID will not display any information that 
can identify the participant.  All of the data collected from the participant will be coded 
using participant study ID and kept in a locked cabinet, and/or password protected 

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computer files. The master list linking participant identifying information to participant 
study data will be kept in a separate, secure location at UNM. Only the UNM study team 
will have access to the master list.  We will keep the link between participant identifying 
information and study data until the end of the research study. This link will only be 
available to UNM, and will not be accessed by researchers at other institutions.
Participant responses to questionnaires will be kept strictly confidential, and dialysis clinic 
staff members will not have any knowledge of the patients’ answers to these 
questionnaires.
 
Data Management: The study team will store all study related data and the database 
secure network servers are sitting behind firewalls and are monitored by network 
personnel on a 24 h/day, 7 days/week basis. Secure access and training of our data entry 
staff will be provided by the study team, and confidentiality of data will be carefully 
maintained. Only study personnel will have access to the secured data.
The investigators will oversee the development of the primary data collection forms. 
Where applicable, data entry screens in the Web-based program will be constructed in the 
same format as printed materials. Data entry will be done directly into the REDCap 
system or similar system at each of the clinical sites. The study staff will coordinate 
online training on the use of the data entry system, data collection procedures, and patient 
confidentiality.
Once a patient is recruited and deemed eligible for the study, to initiate inclusion in the 
web-based tracking system, the University of New Mexico (UNM) will obtain the patient 
profile (name, participant ID, randomization status and contact information). The 
tracking system will monitor enrollment, track follow-up rates, and data entry process, 
and provide up to date status reports. Site coordinators at the clinics will manually enter 
recruit data into a "firewalled" database via the internet.
Documents will be maintained in a locked area and only necessary research personnel 
will have access to this information. Only the participant ID number will be entered into 
the main study database. All research reports, articles, and presentations will present only 
aggregate study findings, and participants will never be identified by name or any other 
personal identifier.
Data will be kept for a minimum of 6 years after study completion in line with federal 
guidelines. PHI and identifiable information will be destroyed 6 years after study closure 
with UNM HSC HRRC. Non-identifiable information will be destroyed after data 
analysis is complete. 
17.Data and Specimen Banking
Neither data nor specimens will be banked for this study.

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18.Risks to Subjects
Hemodialysis:  may be associated with complications. Hemodialysis can lead to low 
blood pressure (25% of all dialysis sessions) which may result in abdominal discomfort, 
nausea, vomiting, muscle cramps, dizziness and anxiety. In addition, hemodialysis can 
lead to bleeding, tachycardia and other abnormal heart rhythms, electrolyte imbalances, 
clotting or infection of the vascular access, and rarely, death. However, the risks 
associated with HD would be present whether or not the patient chooses to participate 
in this study. It is unknown whether use of diuretic and cool dialysate will increase or 
decrease the risk of these complications.
 
Cool dialysate (35.5°): The most common complication for patients dialyzed with cool 
dialysate is feeling colder, and if severe, they may develop shivering. 
Patients will be monitored for patient comfort during dialysis to assess cold 
intolerance that may occur with cool dialysate. If these symptoms are observed, 
then the PI will determine whether this is a safety endpoint.
Bumetanide: Muscle cramps, severe dizziness, and hearing changes, like ringing in the 
ears, are the most common side effects of bumetanide (1.1%). A very serious allergic 
reaction to this drug is also rare.
Patients will be monitored for hypersensitivity reaction or musculoskeletal 
symptoms to determine tolerability of patients to the diuretic. 
 
Psychological: Participants may be asked some questions of a personal nature. They are 
free to decline to answer any question at any time. 
Loss of Privacy: Participation in research may involve a loss of privacy. Steps will be 
taken to mitigate the risk related to confidentiality of study data.
Pregnancy: The risk(s) of cool dialysate and/or Bumetanide on a developing fetus are 
unknown; therefore, subjects who are pregnant or actively planning to become pregnant 
in the next 8 months will not be allowed to participate in this study. 
Subjects of child-bearing potential will have a pregnancy blood test done prior to study 
randomization. Subjects that refuse pregnancy testing will not be allowed to participate in 
this study. 
Nursing Mothers: It is not known whether Bumetanide is excreted in human milk. 
Breast feeding should not be undertaken while the participant is on this drug. Breast 
feeding females will not be allowed to participate in this study.
Hemodialysis Access Site Blood Draws: Infection, bleeding, and damaging the HD 
access site.

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19.Potential Benefits to Subjects
The benefits of this study outweigh the risks. The physical risks and the confidentiality 
risk are low, particularly given the awareness of the study team and the availability of 
supportive staff at the dialysis clinics. The investigators are experienced and the study is 
designed to address feasibility and safety issues. The research burden on all subjects is 
also modest. Participants will have the altruistic satisfaction of helping shape an 
intervention and influence a policy that may be of great value to the more than 300,000 
people in the United States whose lives are prolonged with hemodialysis.
20.Recruitment Methods
The study coordinator will conduct a pre-screening query of the DCI database to identify 
potential study subjects. These subjects will then be approached during their routine 
scheduled HD sessions by a study coordinator to determine their interest in the study. 
21.Provisions to Protect the Privacy Interests of Subjects
Hemodialysis is performed in a common open area with several dialysis stations. 
Face-to-face visits will take place at one of the Albuquerque or the Rio Rancho 
DCI clinic. Every effort will be made to incorporate privacy protections during 
these visits (private room, partitioned area), while DCI eMR will provide any 
required de-identified study information.
22.Economic Burden to Subjects
Responsible Party
Research Procedures
Number of 
Samples/Procedures
Study
3rd Party Payer 
or Participant
Urine Collections
All
Bumetanide or Placebo Administrations
Study Arm 
Dependent
Dialysate at 35.5° C°
Study Arm 
Dependent
Physical Examination
1
     
     
     
     
Responsible Party
Standard of Care Procedures
Number of 
Samples/Procedures
Study
3rd Party Payer 
or Participant
Dialysate at 37°°C
Study Arm 
Dependent
     
     
     
     

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Enrolled subjects will not be charged for any study drugs or study procedures.
23.Compensation
All participants will receive compensation for their time, effort, and involvement in this 
study. If they complete all parts of the study, they will receive a minimum of $250 via a 
re-loadable payment card. Study payment(s) will be uploaded to their card within 24 
hours of completion of a scheduled study event with the exception of weekends and 
holidays. Subjects will receive payment for their study participation per the DIDIT 
Compensation Table:
DIDIT Compensation Table ($250)
Event
Compensation 
Amount
Number of Events
Total 
Compensation
24 hour urine 
collection
$50
3
$150
Phone session 1** 
(Questionnaires)
$30
1
$30
Phone session 2**
(Questionnaires)
$30
1
$30
Phone session 
final** 
(Questionnaires)
$40
1
$40
Additional 
study visits*
$10
Unknown
Unknown
 *If a study participant is required to return to the clinic for research specimen collection, 
they will be compensated in accordance with the DIDIT Compensation Table above.
** Questionnaires may be completed in person or over the phone. 

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24.Compensation for Research-Related Injury
If the enrolled subject is injured or becomes sick as a result of their participation in this 
study, UNMHSC will provide the subject with emergency treatment, at their cost.
No commitment is made by the University of New Mexico Health Sciences Center 
(UNMHSC) to provide free medical care or money for injuries to participants in this 
study.
In the event an enrolled subject has an injury or illness that is caused by their 
participation in this study, reimbursement for all related costs of care will be sought from 
their insurer, managed care plan, or other benefits program. If the enrolled subject does 
not have insurance, they may be responsible for these costs. Enrolled subjects will also be 
responsible for any associated co-payments or deductibles required by their insurance.
It is important for an enrolled subject to tell the investigator immediately if they have 
been injured or become sick because of taking part in this study. 
25.Consent Process
The consent process will take place at Albuquerque DCI Clinics and the Rio Rancho DCI 
clinic. [Hemodialysis is performed in a common open area with several dialysis stations]. 
Potential participants will be approached by DCI staff and asked if they would like to 
hear about a research project that they may be eligible for. If the subject verbalizes 
interest, the DCI staff will then introduce the study coordinator. The potential participant 
will be asked if they agree to discuss the study in an open environment, or if they would 
prefer to discuss the study privately. Study information and the acquisition of informed 
consent will then take place in their environment of choice. Potential subjects may not be 
consented if they choose a private environment and that environment is not available. 
An informed consent form will be used following the guidelines of the Study protocol 
and Institutional Review Board (IRB) and applicable regulations for informed consent. 
Study coordinators will obtain informed consent for the proposed study. Study 
coordinators will contact potential study subjects at the dialysis clinic to describe the 
study and, if they are interested, the subject will be given an unsigned consent form, 
which will include details regarding the voluntary nature of the study, its purpose, 
potential risks and benefits, issues of compensation and expense, and methods to 
confidentiality. At this time or at the next dialysis session, the study coordinator will 
review the consent form with the participant and address any questions or concerns.  All 
potential participants will be given as much time as they need for consent review prior to 
signing an ICF. Prior to signing the consent, potential participants will be asked to 
verbalize the purpose of the study as a check for understanding. The consent form will 
then be signed and dated by the participant before initiation of any study activity. The 

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original signed consent form will be stored in the study file at UNM HSC. A copy of the 
signed consent form will be given to the participant. An additional copy of the consent 
form will be placed in the participant’s DCI medical record.
For potential participants that are identified as Spanish speaking, the same consent 
process described above will be utilized. The process will be completed by one of the 
three Spanish speaking team members approved by the IRB.
Consented subjects who successfully meet all pre-trial criteria will be encouraged, in an 
ongoing basis, to complete the research project.
26.Documentation of Consent
A document of informed consent will be used for this study. A copy of the signed/dated 
consent will be given to the subject. A copy of the signed/dated consent will be placed in 
the subject’s DCI medical record.
27.Study Test Results/Incidental Findings
Participants that complete the study will have a residual renal function review letter sent 
to their Nephrologist. Incidental study findings will not be shared with study participants.
28.Sharing Study Progress or Results with Subjects
Consented subjects will not be provided with a summary of the trial progress while the 
study remains underway nor will they be provided with study results.
29.Inclusion of Vulnerable Populations
No vulnerable populations will be recruited for this study.
30.Community-Based Participatory Research
NA
31.Research Involving American Indian/Native Populations
NA 
32.Transnational Research
NA
33.Drugs or Devices
Neither an IND nor an FDA “IND exemption letter” is needed for this study. 
Bumetanide is an FDA approved loop diuretic. Bumetanide is already being used  as a 
loop diuretic in the Chronic Kidney Disease/End Stage Renal Disease population.

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If the participant is randomized to Bumetanide [3mg], bottled (labeled with subject’s 
name, study ID, instructions) drug will be dispensed from the UNMH investigational 
pharmacy to the research study coordinator monthly. If the participant is not randomized 
to Bumetanide they will be given an equivalent placebo, bottled (labeled with subject’s 
name, study ID, instructions) placebo will be dispensed from the UNMH investigational 
pharmacy to the research study coordinator monthly. The study coordinator will instruct 
the participant on how to take the self-administered study “drug”. The study coordinator 
will be responsible for tracking participant “drug” compliance monthly.
Checklist Section
This section contains checklists to provide information on a variety of topics that require special 
determinations by the IRB.  Please complete all checklists relevant to your research.
I.
Waivers or Alterations of Consent, Assent, and HIPAA Authorization
A. Partial Waiver of Consent for Screening/Recruitment
Complete this checklist if you are requesting a partial waiver of consent so that you 
can review private information to identify potential subjects and/or determine 
eligibility prior to approaching potential subjects for consent or parental permission.
1. Describe the data source that you need to review (e.g., medical records):
Electronic medical records will be accessed at DCI to query for patients that 
meet the study pre-screening criteria: age, date HD was started in order to 
improve chances of a successful study.
2. Describe the purpose for the review (e.g., screening):
Pre-screening: We will need to access and remove the following PHI from 
DCI: patient’s name, age and HD start date. This information will allow us to 
approach eligible participants for their interest in this study. There will be 
minimal risk to the patient as their information will be stored securely off-site 
at UNM and will only be accessible by approved research staff. Records will 
be retained for seven years after study closure, and then destroyed. Study 
information will be kept confidential and will not be reused or shared with 
other entities. 
3. Describe who will conducting the reviews (e.g., investigators, research staff):
UNM research staff will access the DCI database and conduct pre-screening 
reviews. 
Do all persons who will be conducting the reviews already have permitted 
access to the data source?

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 Yes
 No. Explain:      
4. Verify that each of the following are true or provide an alternate justification 
for the underlined regulatory criteria:
a) The activity involves no more than minimal risk to the subjects 
because the records review itself is non-invasive and the results of the 
records review will not be used for any purposes other than those 
described above.
 True
 Other justification:      
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects because eligible subjects will be approached for 
consent to participate in the research and are free to decline.  Further, 
the information accessed during the records review will not be 
disclosed to anyone without a legitimate purpose (e.g., verification of 
eligibility).
 True
 Other justification:      
c) The research could not practicably be carried out without the waiver or 
alteration because there is no other reasonably efficient and effective 
way to identify who to approach for possible participation in the 
research.  
 True
 Other justification:      
d) Whenever appropriate, potentially eligible subjects will be presented 
with information about the research and asked to consider 
participation.  (Regulatory criteria: Whenever appropriate, the 
subjects will be provided with additional pertinent information after 
participation.)
 True
 Other justification:      
Partial Waiver of HIPAA Authorization for Screening/Recruitment
Complete the following additional questions/attestations if the records you will 
review to identify potential subjects and/or determine eligibility include Protected 
Health Information (PHI).

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5. Will you be recording any PHI when conducting the records review to identify 
potential subjects and/or determine eligibility?
 Yes. Describe: We will be recording patient name, age and hemodialysis 
start date.
 No
6. If you answered “Yes” to question 6 above, please describe when you will 
destroy identifiers (must be the earliest opportunity consistent with the 
conduct of the research) or provide justification for why they must be 
retained:
Patients who are being pre-screened through the DCI eMR (DARWIN®) 
database will have the above information collected and stored. If the patient is 
deemed eligible, but declines to consent, this pre-screen information will be 
kept by the research team for seven years after study closure and then 
destroyed. 
7. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 
the Privacy Rule.
 True
 False
B. Waiver of Documentation of Consent
Complete this checklist if you intend to obtain consent verbally but will not be 
obtaining signatures from subjects on a consent form to document consent.  Waivers 
of documentation of consent are commonly requested when using scripts, information 
sheets, or email or survey introductions to present the elements of consent instead of 
using a traditional consent form.
1. Are you requesting a waiver of documentation of consent for some or all 
subjects?
 All
 Some. Explain:      
2. Provide justification for one of the following:
a) That the only record linking the subject and the research would be the 
consent document and the principal risk would be potential harm 
resulting from a breach of confidentiality. Each subject will be asked 

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whether the subject wants documentation linking the subject with the 
research, and the subject's wishes will govern.
     
b) That the research presents no more than minimal risk of harm to 
subjects and involves no procedures for which written consent is 
normally required outside of the research context.
     
3. Do you intend to provide subjects with a written statement regarding the 
research in lieu of a traditional consent form?
 Yes. Please attach a copy to your submission in Click.
 No
C. Alteration of Consent
Complete this checklist if you intend to obtain consent but will be eliminating or 
altering one or more of the required elements of consent. Alterations of consent are 
commonly requested for research involving deception or for minimal risk research 
when an abbreviated consent is desired and one or more of the required element are 
not relevant to the research.
Note: FDA-regulated research is not eligible for an alteration of consent.
1. Which element(s) of consent do you wish to eliminate and why?
     
2. Which element(s) of consent do you wish to alter and why?
     
3. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     
c) The research could not practicably be carried out without the waiver or 
alteration:
     

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d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
D. Full Waiver of Consent/Parental Permission
Complete this checklist if you are requesting a full waiver of consent for all subjects 
or certain subject groups (e.g., retrospective cohort).  Full waivers of consent are 
commonly requested when the research does not include any opportunity for 
interaction with subjects (e.g., chart review).
Note: FDA-regulated research is not eligible for a full waiver of consent using these 
criteria.  If you believe that your FDA-regulated research may be eligible for a waiver 
under another mechanism, such as planned emergency research, contact the HRPO 
for assistance in determining what information to provide to the HRRC.
1. Are you requesting a waiver for some or all subjects?
 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research involves no more than minimal risk to the subjects:
     
b) The waiver or alteration will not adversely affect the rights and 
welfare of the subjects:
     
c) The research could not practicably be carried out without the waiver or 
alteration:
     
d) Whenever appropriate, the subjects will be provided with additional 
pertinent information after participation:
     
E. Full Waiver of Consent/Parental Permission (Public Benefit or Service 
Programs)
Complete this checklist if you are requesting a full waiver of consent for all subjects 
or certain subject groups (e.g., retrospective cohort) and the research involves the 
evaluation of a public benefit or service program.  
1. Are you requesting a waiver for some or all subjects?

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 All
 Some. Explain:      
2. Provide justification for each of the following regulatory criteria:
a) The research or demonstration project is to be conducted by or subject 
to the approval of state or local government officials and is designed to 
study, evaluate, or otherwise examine: (i) public benefit or service 
programs; (ii) procedures for obtaining benefits or services under those 
programs; (iii) possible changes in or alternatives to those programs or 
procedures; or (iv) possible changes in methods or levels of payment 
for benefits or services under those programs:
     
b) The research could not practicably be carried out without the waiver or 
alteration.
     
F. Full Waiver of HIPAA Authorization
Complete this checklist if you are requesting a full waiver of the requirement to 
obtain HIPAA authorization for all subjects or certain subject groups (e.g., 
retrospective cohort).  Full waivers of HIPAA authorization are commonly requested 
when the research does not include any opportunity for interaction with subjects 
(e.g., chart review).
1. Are you requesting a waiver of authorization for some or all subjects?
 All
 Some. Explain:      
2. Describe your plan to protect health information identifiers from improper use 
and disclosure:
     
3. Describe your plan to destroy identifiers at the earliest opportunity consistent 
with conduct of the research (absent a health or research justification for 
retaining them or a legal requirement to do so):
     
4. Describe why the research could not practicably be conducted without the 
waiver or alteration:
     

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5. The PHI accessed or recorded for identification/screening purposes will not be 
reused or disclosed to (shared with) any other person or entity, except as 
required by law, for authorized oversight of the research study, or for other 
research for which the use or disclosure of the PHI would be permitted under 
the Privacy Rule.
 True
 False
G. Other Waiver Types
If you are seeking another waiver type (e.g., Planned Emergency Research, Waiver of 
Parental Permission to Protect Child Participants, Enforcement Discretion for In 
Vitro Diagnostics, etc. contact the HRPO office for assistance in determining what 
information to submit for the HRRC’s consideration.
II. Vulnerable Populations
A. Adults with Cognitive Impairments
Complete this checklist if the subject population will include adults with cognitive 
impairments.  
This checklist does not need to be completed if the research doesn’t involve 
interactions or interventions with subjects and will be conducted under a waiver of 
consent.
1. Describe why the objectives of the study cannot be met without inclusion of 
adults with cognitive impairments.
     
2. Describe how capacity to consent will be evaluated.
     
3. If subjects may regain capacity to consent, or if subjects may have fluctuating 
capacity to consent, describe your plans to evaluate capacity to consent 
throughout the research and to obtain consent to continue participation if 
capacity is regained.
     
4. Describe your plans, if any, to provide information about the research to 
subjects and the steps you will take to assess understanding.
     

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5. Describe your plans to obtain assent, including whether assent will be 
obtained from none, some, or all subjects.
     
6. Describe why risks to subjects are reasonable in relation to anticipated 
benefits to the subjects.
     
7. If this study involves a health or behavioral intervention, describe why the 
relation of the anticipated benefit to the risk of the research is at least as 
favorable to the subjects as that presented by alternative procedures.
     
8. Describe your plans for monitoring the well-being of subjects including any 
plans to withdraw subjects from the research if they appear to be unduly 
distressed.
     
B. Children
Complete this checklist if the subject population will include children.
1. Select the category of research that you believe this research falls within and 
provide justification for any associated criteria.  If there are different 
assessments for different groups of children or arms (e.g., placebo vs. drug), 
include a memo to provide an assessment for each group.  
 Research not involving greater than minimal risk. (Minimal risk means 
that the probability and magnitude of harm or discomfort anticipated 
in the research are not greater in and of themselves than those 
ordinarily encountered in daily life or during the performance of 
routine physical or psychological examinations or tests.)
 Research involving greater than minimal risk but presenting the 
prospect of direct benefit to the individual subjects.
Provide justification for each of the following criteria:
(1) The risk is justified by the anticipated benefit to the subjects:
     
(2) The relation of the anticipated benefit to the risk is at least as 
favorable to the subjects as that presented by available 
alternative approaches:
     

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 Research involving greater than minimal risk and no prospect of direct 
benefit to individual subjects, but likely to yield generalizable 
knowledge about the subject's disorder or condition.
Provide justification for each of the following criteria:
(1) The risk represents a minor increase over minimal risk:
     
(2) The intervention or procedure presents experiences to subjects 
that are reasonably commensurate with those inherent in their 
actual or expected medical, dental, psychological, social, or 
educational situations:
     
(3) The intervention or procedure is likely to yield generalizable 
knowledge about the subjects' disorder or condition which is of 
vital importance for the understanding or amelioration of the 
subjects' disorder or condition
     
C. Pregnant Women and Fetuses
Complete this checklist if the subject population will include pregnant women and 
fetuses.
This checklist does not need to be completed if the research is both minimal risk and 
is not conducted, funded, or otherwise subject to regulation by DHHS, DOD, or EPA.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical studies, including studies on 
pregnant animals, and clinical studies, including studies on non-pregnant 
women, have been conducted and provide data for assessing potential risks to 
pregnant women and fetuses.
     
2. The risk to the fetus is caused solely by interventions or procedures that hold 
out the prospect of direct benefit for the woman or the fetus; or, if there is no 
such prospect of benefit, the risk to the fetus is not greater than minimal and 
the purpose of the research is the development of important biomedical 
knowledge which cannot be obtained by any other means.
     
3. Any risk is the least possible for achieving the objectives of the research.
     

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D. Neonates of Uncertain Viability or Nonviable Neonates
Complete this checklist if the subject population will include neonates of uncertain 
viability.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     
4. The research holds out the prospect of enhancing the probability of survival of 
the neonate to the point of viability, and any risk is the least possible for 
achieving that objective, or, the purpose of the research is the development of 
important biomedical knowledge which cannot be obtained by other means 
and there will be no added risk to the neonate resulting from the research
     
E. Nonviable Neonates
Complete this checklist if the subject population will include nonviable neonates.
Provide justification for each of the following:
1. Where scientifically appropriate, preclinical and clinical studies have been 
conducted and provide data for assessing potential risks to neonates.
     
2. Each individual providing consent is fully informed regarding the reasonably 
foreseeable impact of the research on the neonate.
     
3. Individuals engaged in the research will have no part in determining the 
viability of a neonate.
     

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4. The purpose of the research is the development of important biomedical 
knowledge that cannot be obtained by other means.
     
Verify each of the following:
5. Vital functions of the neonate will not be artificially maintained
 True
 False
6. The research will not terminate the heartbeat or respiration of the neonate
 True
 False
7. There will be no added risk to the neonate resulting from the research
 True
 False
F. Biomedical and Behavioral Research Involving Prisoners
Complete this checklist if the subject population will include prisoners.
Note: Minimal risk for research involving prisoners is the probability and magnitude 
of physical or psychological harm that is normally encountered in the daily lives, or 
in the routine medical, dental, or psychological examination of healthy persons.
1. Select and justify which allowable category of research involving prisoners 
this research falls within:
 Study of the possible causes, effects, and processes of incarceration, and of 
criminal behavior, provided that the study presents no more than minimal 
risk and no more than inconvenience to the subjects
     
 Study of prisons as institutional structures or of prisoners as incarcerated 
persons, provided that the study presents no more than minimal risk and 
no more than inconvenience to the subjects
     
 Research on conditions particularly affecting prisoners as a class (for 
example, vaccine trials and other research on hepatitis which is much 
more prevalent in prisons than elsewhere; and research on social and 
psychological problems such as alcoholism, drug addiction, and sexual 
assaults)

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 Research on practices, both innovative and accepted, which have the intent 
and reasonable probability of improving the health or well-being of the 
subject
     
 Epidemiologic studies in which the sole purpose is to describe the 
prevalence or incidence of a disease by identifying all cases or to study 
potential risk factor associations for a disease, the research presents no 
more than Minimal Risk and no more than inconvenience to the subjects, 
and Prisoners are not a particular focus of the research.
     
2. Provide justification for each of the following regulatory criteria:
a) Any possible advantages accruing to the prisoner through his or her 
participation in the research, when compared to the general living 
conditions, medical care, quality of food, amenities and opportunity 
for earnings in the prison, are not of such a magnitude that his or her 
ability to weigh the risks of the research against the value of such 
advantages in the limited choice environment of the prison is impaired
     
b) The risks involved in the research are commensurate with risks that 
would be accepted by non-prisoner volunteers
     
c) Procedures for the selection of subjects within the prison are fair to all 
prisoners and immune from arbitrary intervention by prison authorities 
or prisoners. Unless justification is provided, control subjects must be 
selected randomly from the group of available prisoners who meet the 
characteristics needed for that particular research project
     
d) The information is presented in language which is understandable to 
the subject population
     
e) Adequate assurance exists that parole boards will not take into account 
a prisoner's participation in the research in making decisions regarding 
parole, and each prisoner is clearly informed in advance that 
participation in the research will have no effect on his or her parole

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f)
When appropriate, adequate provision has been made for follow up 
examination or care after research participation, taking into account 
the varying lengths of individual prisoners' sentences, and for 
informing participants of this fact
     
III.Medical Devices
Complete this checklist if the research evaluates the safety or effectiveness of a medical device.  
If more than one medical device is being evaluated, provide the requested information for each.
A. Device Name:       
B. Manufacturer:       
C. Does the research involve a Significant Risk Device under an IDE?
 Yes. Include documentation of the FDA approval of the IDE with your submission.  
Acceptable methods of documentation include: (1) FDA letter noting IDE number 
and approval status; (2) Industry sponsor letter noting IDE number and FDA 
approval status; or (3) FDA-approved industry sponsor protocol with IDE number 
noted 
 No
D. Is the research IDE-exempt?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is IDE-exempt or a letter from the sponsor (or sponsor-investigator) 
justifying why they believe the research is IDE-exempt*.  
 No
E. Does the research involve a Non-Significant Risk (NSR) Device?
 Yes. Include a FDA letter with your submission noting the determination that the 
research is NSR or a letter from the sponsor (or sponsor-investigator) justifying why 
they believe the research is NSR**.  
 No
* This FDA guidance includes a description for when a device study is exempt from the 
IDE requirements: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM127067.pdf 

DIDIT: Diuretic/Cool Dialysate Trial
   
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**This FDA guidance includes information on how to differentiate between Significant 
Risk and Non-Significant Risk device studies: 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf