Efficacy and Safety of GLP-1 Agonist Therapy in Overweight and Obese Subjects With Cystic Fibrosis-related Diabetes: a Pilot Study
Phase: PHASE2
Conditions: Cystic Fibrosis, Cystic Fibrosis-related Diabetes
Sponsor: University of Minnesota

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
Page 1 of 40 
Template Revised On: 10/28/2022 
ANCILLARY REVIEWS 
DO NOT DELETE.  Submit the completed checklist below with your protocol. 
Which ancillary reviews do I need and when do I need them? 
Refer to HRP-309 for more information about these ancillary reviews. 
Select yes or 
no 
Does your study… 
If yes… 
Impact on 
IRB Review 
☐ Yes 
☒ No 
 
Include Gillette resources, 
staff or locations 
Gillette Scientific review and Gillette 
Research Administration approval is 
required.  Contact: 
research@gillettechildrens.com   
Required 
prior to IRB 
submission 
☒ Yes 
☐ No 
 
Involve Epic, or Fairview 
patients, staff, locations, or 
resources? 
The Fairview ancillary review will be 
assigned to your study by IRB staff 
Contact: ancillaryreview@Fairview.org 
Approval 
must be 
received 
prior to IRB 
committee
/ 
designated 
review.   
 
Consider 
seeking 
approval 
prior to IRB 
submission
. 
☒ Yes 
☐ No 
 
Include evaluation of drugs, 
devices, biologics, tobacco, or 
dietary supplements or data 
subject to FDA inspection? 
The regulatory ancillary review will be 
assigned to your study by IRB staff 
Contact: medreg@umn.edu  
 
See: 
https://policy.umn.edu/research/indid
e  
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Require Scientific Review? Not 
sure?  See guidance in the 
Investigator Manual (HRP-
103). 
 
Documentation of scientific merit must 
be provided.   
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screening/prevention, or 
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Application and follow instructions on 
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from these 
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s must be 
received 
prior to IRB 
approval;  
 
These 
groups 
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Use the Center for Magnetic 
Resonance Research (CMRR) 
or MR from Masonic Institute 
for the Developing Brain 
(MIDB) as a study location? 
Complete the CMRR pre-IRB ancillary 
review  
Contact: ande2445@umn.edu  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
Page 2 of 40 
Template Revised On: 10/28/2022 
☐ Yes 
☒ No 
 
Include the use of 
recombinant or synthetic 
nucleic acids, toxins, or 
infectious agents? 
Complete the IBC application via 
eprotocol.umn.edu 
 
each have 
their own 
application 
process.  
☐ Yes 
☒ No 
Include the use of human fetal 
tissue, human embryos, or 
embryonic stem cells? 
Contact OBAO for submission 
instructions and guidance 
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Include PHI or are you 
requesting a HIPAA waiver? 
If yes, HIPCO will conduct a review of 
this protocol. 
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services, and/or have an IND, IDE, 
or designated NSR-IDE by the 
UMN IRB? 
The CTSI monitoring ancillary review 
will be assigned to your study by IRB 
staff. 
Please note eligibility criteria here. 
Contact: fencl003@umn.edu 
Approval 
must be 
received 
prior to IRB 
approval. 
 
These 
groups do 
not have a 
separate 
application 
process but 
additional 
informatio
n from the 
study team 
may be 
required. 
 
☐ Yes 
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Practices Integrated 
Informatics Core? 
 
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Exchange (IE)? 
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review will be assigned to your study 
by IRB staff 
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Pham0435@umn.edu 
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Does not 
affect IRB 
approval. 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Template Revised On: 10/28/2022 
PROTOCOL COVER PAGE 
 
Protocol Title 
Efficacy and safety of GLP-1 agonist therapy in overweight and 
obese subjects with cystic fibrosis-related diabetes: a pilot study 
Principal 
Investigator/Faculty 
Advisor 
Name: Amir Moheet 
Affiliation:  ☒UMN   ☐Fairview   ☐ Gillette 
UMN Home Department: Medicine, Division of Diabetes, 
Endocrinology and Metabolism 
UMN Home Dept ID: 11768 
Telephone Number: 
Email Address: mohee002@umn.edu 
Scientific Assessment 
Nationally based non-federal funding organizations 
IND/IDE # (if 
applicable) 
 IND 165316 
IND/IDE Holder 
Amir Moheet, MBBS 
Investigational Drug 
Services # (if 
applicable) 
6127 
Version 
Number/Date: 
Version 5.1, 09 Aug 2024 
 
 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
Page 4 of 40 
Template Revised On: 10/28/2022 
 
REVISION HISTORY 
 
Revision # 
Version Date 
Summary of Changes 
Consent Change? 
1.1 
19 APR 2023 
Changes made in response to 4/7/23 
IRB letter 
Y 
1.2 
22Sep2023 
Changes made per DSMB 
recommendations, added IDS #, 
updated participant reimbursement 
to include mileage – added federal 
mileage reimbursement rate  
Y 
1.3 
09Oct2023 
OGTT protocol language and schedule 
of events table clarified 
Y 
1.4 
17Nov2023 
Use of MacCAT-CR specifically 
indicated per IRB stip when 
appropriate, instead of shorter 
UBACC tool per Courtney Jarboe 
upon review 12/20/23 of this MOD 
and original IRB analyst’s 
Modifications Required Letter dated 
13Nov2023 
N 
2.0 
30Nov2023 
PHQ-9 language, CGM start changed 
from Week 10 to week 8, and 
schedule of events updated 
Y 
3.0 
21Dec2023 
MacCAT-CR language clarified to 
match intended meaning of IRB stip 
for Revision 1.4  
N 
4.0 
31Jan2024 
Updated inclusion criteria – insulin 
therapy removed 
Y 
5.0 
28Mar2024 
Updates per CR stips letter dated 
22Mar2024 
Y 
5.1 
09Aug2024 
Updated monitoring language added 
per HRPP audit report 7/31/2024. 
Y 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Template Revised On: 10/28/2022 
Table of Contents 
 
1.0 
Objectives .......................................................................................................................... 7 
2.0 
Background ........................................................................................................................ 7 
3.0 
Study Endpoints/Events/Outcomes ................................................................................ 10 
4.0 
Study Intervention(s)/Investigational Agent(s) ............................................................... 11 
5.0 
Procedures Involved ........................................................................................................ 11 
6.0 
Data and Specimen Banking ............................................................................................ 16 
7.0 
Sharing of Results with Participants ................................................................................ 17 
8.0 
Study Population ............................................................................................................. 17 
9.0 
Vulnerable Populations ................................................................................................... 18 
10.0 
Local Number of Participants .......................................................................................... 21 
11.0 
Local Recruitment Methods ............................................................................................ 21 
12.0 
Withdrawal of Participants .............................................................................................. 22 
13.0 
Risks to Participants ........................................................................................................ 23 
14.0 
Potential Benefits to Participants .................................................................................... 26 
15.0 
Statistical Considerations ................................................................................................ 26 
16.0 
Health Information and Privacy Compliance .................................................................. 28 
17.0 
Confidentiality ................................................................................................................. 32 
18.0 
Provisions to Monitor the Data to Ensure the Safety of Participants ............................. 33 
19.0 
Provisions to Protect the Privacy Interests of Participants ............................................. 36 
20.0 
Compensation for Research-Related Injury .................................................................... 37 
21.0 
Consent Process .............................................................................................................. 37 
22.0 
Setting .............................................................................................................................. 38 
23.0 
Multi-Site Research ......................................................................................................... 38 
24.0 
Coordinating Center Research ........................................................................................ 38 
25.0 
Resources Available ......................................................................................................... 38 
26.0 
References ....................................................................................................................... 39 
 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
Page 6 of 40 
Template Revised On: 10/28/2022 
 
ABBREVIATIONS/DEFINITIONS 
● CF-cystic fibrosis 
● GLP-1RA-Glucagon like peptide 1 receptor agonist 
● CFRD -Cystic fibrosis related diabetes 
● CFTR-cystic fibrosis transmembrane conductance regulator 
● ETI- Elexacaftor/Tezacaftor/Ivacaftor 
● OGTT-oral glucose tolerance test and on glycemic outcomes as measured by  
● CGM-continuous glucose monitoring  
● SC-subcutaneous  
● SMBG-self-measured blood glucose 
● AE -adverse effects 
● AUC-Area under the curve  
● BMI-body mass index  
● CFQ-R- Cystic Fibrosis Questionnaire-Revised 
● CRF-case report forms 
● CVD-cardiovascular disease  
● DHQ- Diet History Questionnaire 
● DPP-4- dipeptidyl peptidase-4 
● DSMB-Data safety and monitoring board  
● FEV1-Forced expiratory volume 
● GI-gastroenterology  
● GIP- glucose-dependent insulinotropic polypeptide 
● PHQ-9-Patient Health Questionnaire-9 
● MacCAT-CR - MacArthur Competence Assessment Tool for Clinical Research 
● UBACC - Revised University of California, San Diego Brief Assessment of Capacity to 
Consent 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Template Revised On: 10/28/2022 
1.0 
Objectives 
1.1 Purpose: 
The overall goal of this proposal is to collect pilot data for safety and feasibility 
metrics to support a future larger randomized controlled trial. In this study, we 
will examine the safety and tolerability of GLP-1RA semaglutide for 
overweight/obese adult patients with CFRD.  We hypothesize that weekly 
administration of the long-acting GLP-1RA semaglutide to overweight/obese 
CFRD patients will be safe and well tolerated.  
Specific Aim 1: Collect pilot data on the safety and feasibility of weekly 
semaglutide therapy in overweight and obese patients with CFRD to support a 
future larger randomized controlled trial. 
Hypothesis 1: Weekly therapy with GLP-1RA semaglutide will be safe and well 
tolerated in overweight/obese adults with CFRD.  
Specific Aim 2: Collect preliminary data to examine the impact of semaglutide 
therapy on insulin secretion, glucagon and glucose levels as measured by oral 
glucose tolerance test (OGTT), and on glycemic outcomes as measured by 
continuous glucose monitoring (CGM) and HbA1c. 
Hypothesis 2a: Treatment with semaglutide will lower glucose levels, and increase 
insulin and C-peptide area under the curve (AUC) during the OGTT as compared 
to baseline.  
Hypothesis 2b: Treatment with semaglutide will improve glycemic control as 
indicated by time in range on CGM and HbA1c 
2.0 
Background 
2.1 Significance of Research Question/Purpose: 
Increasing prevalence of overweight/obesity in CF: CF has classically been associated 
with malnutrition and being underweight 1.  A high calorie  diet has been the standard 
of care for several decades, to offset the negative energy expenditure created by 
malabsorption, increased work of breathing, chronic inflammation, and pulmonary 
exacerbations 2. Intense emphasis on nutritional augmentation and advancement in 
medical therapies including recent introduction of CFTR modulators have significantly 
reduced the prevalence of malnutrition in CF. However, this success has been 
accompanied by a significant rise in overweight/obesity in CF, which is beginning to 
resemble the global trend of obesity in the general population. In 2005, Kastner-Cole et 
al 3 reported the prevalence of overweight and obesity in patients with CF 
(homozygous ΔF508) in the United Kingdom to be 9.1% and 1.1%, respectively. In this 
study, there was a positive association between BMI and FEV1 in adults up to BMI of 23 
kg/m2. Stephenson et al.4 evaluated longitudinal changes in nutrition at the Toronto CF 
Center, comparing the adult nutritional status from before 1990 to after 2000. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Underweight decreased from 20.6% to 11.1% while overweight/obese increased from 
7% to 18.4%.   According to the 2019 US CF Foundation registry report 23.1% of adults 
with are overweight and 8.3% are obese and the prevalence of adult 
overweight/obesity has more than doubled since 19995. In a recent cross-sectional 
analysis of 484 adults with CF seen at the U of MN CF Center between 2015-2017, we 
reported that 25.6% of patients were overweight and 6.6% were obese 6. It was 
particularly striking that 25% of patients with severe CF mutations had BMI in the 
overweight/obese category. Overweight and obese patients in our CF cohort were 
more likely to have hypertension and higher levels of total cholesterol, LDL-cholesterol 
and triglyceride. 
 
CFTR modulator therapies target the underlying defect causing CF, so may reduce the 
factors that historically drove under-nutrition in CF. In fact, many studies have 
demonstrated weight gain in modulator-treated patients. A recent systematic review 
examined 13 CFTR modulator trials between 2012-2017 found strong evidence for 
weight gain in Ivacaftor-treated patients with a G511D mutation, but weaker evidence 
for weight gain with Lumacaftor/Ivacaftor or Tezacaftor/Ivacaftor treatment 7.  
Elexacaftor/Tezacaftor/Ivacaftor (ETI), approved in late 2019, was not included in the 
systematic review. ETI is a “highly effective” CFTR modulator for individuals with 
eligible CFTR variants, providing similar level of CFTR function as Ivacaftor. While 
longitudinal data for ETI is not available, in single-center study of 94 adults, we 
reported an average of 2.4% increase in weight after 3 months of ETI therapy 8. 
 
Is obesity harmful in CF? Traditionally, because of concern about the known deleterious 
impact of undernutrition, because it was difficult for CF patients to gain and maintain 
weight, and because there was no evidence of cardiovascular disease in this 
population, CF patients were encouraged to eat extra calories and gain weight, without 
a weight “ceiling”. In the past we showed that there was no additional pulmonary 
advantage for BMI greater than 28-29 6.  Recently, evidence is emerging that 
overweight/obesity may have a negative impact on patients with CF. In the general 
population, there is a well-known association between obesity and CVD. We have 
recently shown that overweight and obese patients at the UMN CF Center are more 
likely to have hypertension and higher levels of total cholesterol, LDL-cholesterol and 
triglyceride, and have found a handful of patients who have had a myocardial 
infarction, which has not previously been reported in CF. There are not enough data to 
say whether other problems known to be associated with obesity in the general 
population might also emerge in CF, but it is certainly plausible to assume that 
problems like decreased lung function, joint problems, liver steatosis/cirrhosis, and 
cancer might aggravate conditions already associated with CF. Thus, there is rationale 
to explore the safety and efficacy of treatments that promote weight loss in CF. 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
Page 9 of 40 
Template Revised On: 10/28/2022 
Role of incretin therapy for obesity: Besides type 2 diabetes, GLP-1 RA are also 
approved for treatment of obesity.  Incretin hormones have been shown to play a role 
in regulation of appetite and food intake 9. The mechanism whereby peripherally 
administered GLP-1 inhibits food intake is not clear. GLP-1 receptors are expressed in 
many regions of the brain and in particular in the arcuate nucleus and other 
hypothalamic regions involved in them regulation of food intake 9. It has been 
postulated that GLP-1 effect on appetite could be through interaction with sensory 
neurons in the gastrointestinal tract or central effect on the brain. In clinical trials, GLP-
1RA were shown to lower body weight by reducing appetite and hunger, increasing 
satiety and reducing food cravings 10. Childhood eating habits strongly influence adult 
eating behaviors in general population studies, which suggests that overweight/obese 
people with CF may have difficulty transitioning to a lower-calorie diet after a lifetime 
of consuming high-calorie, high-fat foods. Therefore, GLP-1RA therapy would be an 
attractive therapeutic option in obese and overweight patients with CF.   
 
Role of incretin hormones in the pathogenesis of dysglycemia in CF: The 
pathophysiology underlying the development of glucose intolerance and CFRD in 
subjects with CF is multifactorial and not fully understood. The earliest insulin defect 
seen in CF is loss of first-phase insulin response with post prandial hyperglycemia. This 
pattern suggests dysregulation in the incretin hormone axis. GLP-1 and GIP are incretin 
hormones released by intestinal cells in response to ingestion to meal. The primary 
actions of incretin hormones are to stimulate insulin secretion and to inhibit glucagon 
secretion, thereby lowering post-prandial glucose excursions 9.  Previous studies have 
examined the role of incretin hormones in CF related glucose intolerance. In one study, 
GLP-1 was found to be significantly lower in patients with CF and CFRD compared to in 
healthy controls 11. In another study, Perano et al 12 showed that pancreatic enzyme 
replacement therapy improved GLP-1 and GIP secretion and postprandial glycemia. In a 
small study of subjects with CF and pancreatic insufficiency and impaired glucose 
tolerance, treatment with GLP-1 RA showed improvement in post-prandial glucose 
excursion, primarily due to slower gastric emptying 13. Both GIP and GLP-1 are rapidly 
degraded by the aminopeptidase protease dipeptidyl peptidase-4 (DPP-4). In a recent 
study Kelly et al examined the effect of sitagliptin (a DPP-4 inhibitor) on various 
measures of β-cell function and glycemia in CF with abnormal glucose tolerance 14. 
Sitagliptin intervention in this study augmented meal-related incretin responses with 
improved early insulin secretion and glucagon suppression without affecting post-
prandial glycemia. These studies provide data to support the role of incretin hormones 
in CF related dysglycemia and provide strong rationale to further investigate these 
drugs in the treatment of CFRD. 
 
Novel pharmacological strategies are needed CFRD management in setting of 
overweight/obesity: CFRD is the most common extra pulmonary complication of CF and 
was identified by the CF community as one of the top priorities for CF research. Insulin 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Template Revised On: 10/28/2022 
is the treatment of choice for CFRD and is associated with improvement in glycemic 
control, nutritional status and lung function15. However, in the current era of highly 
effective CFTR modulator therapies and increasing prevalence of overweight/obesity in 
CF, there is urgent need to develop novel pharmacological strategies for management 
of CFRD. Many patients with CFRD are now also developing a phenotype of type 2 
diabetes with obesity, insulin resistance and high insulin requirement. In clinical 
practice, medications approved for type 2 diabetesare increasingly being used for 
treatment of CFRD . However, there is limited clinical trial data to recommend the use 
of these medications. We found that 61% of the patients with CFRD followed at U of 
MN have BMI >25.  Semaglutide, a GLP-1RA administered weekly through 
subcutaneous (SC) injection has been FDA approved for management of type 2 
diabetes and obesity. It is highly effective in improving glycemic control and inducing 
weight loss. It has been widely studied in trials of type 2 diabetes and obesity and 
found to be safe and well tolerated. GLP1 –RA therapy can provide an effective 
treatment option for this emerging and important clinical problem of CFRD 
complicated by obesity. 
2.2 Preliminary Data:  
There are no clinical trial data on chronic use of GLP-1RA in CFRD. In a small study of 
6 patients (average age 17 yrs) with CF and impaired glucose tolerance, a single dose of 
exenatide (GLP-1RA) was shown to acutely improve post prandial glycemia compared 
to placebo 13.  CF patients with pancreatic insufficiency have been shown to have 
impaired secretion of GLP-1 and higher postprandial glucose excursions compared to 
healthy controls 11,16. Pancreatic enzyme replacement therapy has been shown to 
improve GLP-1 secretion and improve postprandial hyperglycemia in CF patients 
compared to control 11. In a published single case report, the GLP-1RA semaglutide in 
combination with basal insulin for 3 months improved glycemic control and induced 
weight loss without significant GI side effects. In this patient with pancreatic 
insufficiency, serial pancreatic enzyme measurements did not change and there was 
improvement in fasting c-peptide level post treatment with semaglutide17. These small 
studies suggest a possible role of incretin-based therapies in CFRD.  
Existing Literature: 
                       See section 2.1 
3.0 
Study Endpoints/Events/Outcomes 
3.1 Primary Endpoint/Event/Outcome:  
The primary outcomes are related to feasibility, including safety and treatment 
tolerability. Safety will be evaluated as the proportion (in %) of participants who 
experience a serious adverse event during the study. Tolerability will be evaluated 
as the proportion (in %) of participants who discontinue their assigned treatment 
due to side effects. 
3.2 Secondary Endpoint(s)/Event(s)/Outcome(s):  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Template Revised On: 10/28/2022 
Secondary outcomes will be change in glucose and insulin area under the curve 
during the OGTT and the time to peak insulin level. Additional secondary outcome 
measures include time in range, glycemic variability and time below range based 
on CGM,  HbA1c,  moderate/mild adverse events and insulin dose (IU/day for 
both bolus and basal). 
4.0 
Study Intervention(s)/Investigational Agent(s) 
4.1 Description:  
Semaglutide (Ozempic®) is a GLP-1RA, which is given as a self-administered 
weekly SC injection. Semaglutide is FDA approved for treatment of type 2 
diabetes and obesity.  Semaglutide will be initially started at 0.25 mg weekly 
dose. The weekly dose will be increased to 0.5 mg at the 4 week time point and to 
1 mg at 8 weeks (as per manufacturer prescribing information). Semaglutide 
doses will be titrated up to and kept on the target 1 mg weekly dose until the end 
of the study. Subjects who cannot tolerate the 1 mg dose will be maintained at 
the maximum tolerated dose. Participants will receive treatment for a total of 12 
weeks. Study drug will be discontinued at the end of the study. Participants will 
not permitted to start any other new diabetes medication (besides insulin) during 
the study period.  
 
Safety will be assessed as the proportion of enrolled participants who experience 
severe adverse events (AE).  Tolerability will be evaluated as the proportion (in %) 
of participants who discontinue their assigned treatment due to side effects. We 
will collect data on consent rate (proportion of all participants who were contacted 
and eligible who consented), and completion rate (proportion of subjects who 
complete all study visits).    
4.2 Drug/Device Handling:  
• IND to be shipped to, stored, logs maintained, and dispensed per Fairview 
Health Services Investigational Drug Policy. 
• IDS# 6127 
4.3 Biosafety:  
Not applicable  
4.4 Stem Cells:  
Not applicable 
4.5 Fetal Tissue:  
    
Not applicable          
5.0 
Procedures Involved 
5.1 Study Design:  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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This open label, single arm pilot study, will examine the safety and tolerability of 
GLP-1RA semaglutide for overweight/obese adult patients with CFRD.   
5.2 
Study Procedures:  
Study protocol:  Participants will be recruited from UMN CF center. The screening and 
recruitment process is reviewed later in sections 8 and 11 respectively. After completing 
baseline labs, CGM monitoring and OGTT (table 1), subjects will be started on 
semaglutide 0.25 mg given as self-administered weekly SC injections. Standard 
checklist will be developed to titrate semaglutide dose using the manufacturer 
prescribing information and adverse effects criteria as reviewed in the DSMB plan. 
Subjects will be initially started on semaglutide 0.25 mg weekly. The weekly dose will 
be increased to 0.5 mg at the 4 week time point and to 1 mg at 8 weeks (as per 
manufacturer prescribing information). Dose will be titrated down to the next lower dose 
if subject experiences moderate adverse effects (AE) and medication will be 
discontinued if severe AE are experienced.  AE criteria are reviewed in DSMB plan (See 
Section 15.2). Semaglutide dose will be titrated up to and kept on the target 1 mg weekly 
dose till the end of the study. Subjects who cannot tolerate the 1 mg dose will be 
maintained at the maximum tolerated dose.  To reduce the risk of hypoglycemia in 
subjects on insulin therapy, doses of bolus and basal insulin will be reduced by 20% at 
the time of initiation of semaglutide treatment. Patients will not be allowed to change the 
type of insulin delivery (daily insulin injections vs insulin pump) during the study 
period. Patients will continue with their usual method of glucose monitoring including 
self-measured blood glucose (SMBG) using finger sticks or personal CGM.  Participants 
will not permitted to start any other new diabetes medication (besides insulin) during the 
study period. If applicable,the insulin dose will be adjusted in accordance with SMBG 
and personal CGM readings. In accordance with the current guidelines 15, the treatment 
targets are fasting or premeal glucose between 70 and 130 mg/dl, and 2–3 h post-
prandial glucose <180 mg/dl. For patient utilizing personal CGM, the treatment targets 
will be a glucose time-in-range (70-180 mg/dl) greater than 70% of the time, 
hypoglycemia (glucose <70mg/dl) <4% of the 
time, and major hypoglycemia (glucose <54 
mg/dl) <1% of the time 18. Glycemic data will 
be reviewed at all study visits and telephone 
contacts (figure 1) after the initial of therapy and 
if applicable insulin doses will be adjusted as 
needed. As a general guideline basal insulin 
would be reduced by 10% for fasting 
hypoglycemia on finger stick glucose reading < 
70 mg /dL or glucose < 70 mg/dl for > 15 
minutes on CGM.   Basal insulin would be 
reduced by 15% for fasting hypoglycemia on 
finger stick glucose reading < 54 mg /dL or 
glucose < 54 mg/dl for >15 minutes on CGM. 
For Post meal hyperglycemia preceding insulin 
bolus dose would be increased by 10% if there 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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is pattern of 2 hour post meal glucose readings between 181 and 250 mg/dl on finger 
stick or in the 181-250 range for > 15 minute on CGM. If there is pattern of 2 hour post 
meal readings  > 250 mg/dl on finger stick or > 250 mg/dl for > 15 minutes preceding 
insulin bolus dose would be increased by 15 %. If applicable, insulin dose adjustment 
would be at the discretion of the study investigator to maintain the glucose readings in 
the target range. Investigator will also take into account other factors such as any missed 
insulin dose or timing of meal bolus. Participants will receive treatment for a total of 12 
weeks. Study drug will be discontinued at the end of the study. If applicable, insulin will 
be adjusted at week 12 at the end of the study and during telephone visit at week 13 to 
return to baseline.  
 
Five visits (figure 1) to the study center will be scheduled (weeks -2, 0, 4, 8 and 12) at 
which information will be collected  about concomitant medications, if applicable basal 
and bolus insulin doses , any GI side effects, body weight, blood pressure, and heart rate. 
Number of hypoglycemic events will be monitored and captured based on the American 
Diabetes Association definitions of hypoglycemia. Study visit 1 could occur at CSC, 
DCRU or CRU. Visits 2, 3, 4 and 5 will occur at CRU. OGTT will performed at visit 2 
before starting semaglutide and repeated at the end of the study. Blood samples (around 
20-40mL) will be collected at Visit 2 and 5 for lipase, electrolytes, HbA1c, liver 
function and renal function; and at Visit 3 and 4 for electrolytes and renal function. 
Serum pregnancy test will be done at visit 1 prior to treatment initiation for all subjects 
who could become pregnant. Urine pregnancy testing will be done at visits 2, 3, and 4. 
These participants must agree to take precautions that are effective in preventing 
pregnancy throughout this study, which could include complete abstinence from sexual 
intercourse; oral, injectable, or implanted hormonal contraceptives; intrauterine device; 
or tubal ligation 
 
Semaglutide will be started at visit 2 (week 0) and the patient will self-administer the 
first dose in the clinical research unit. Following data would be collected at the 
enrollment: age, sex, date of birth, diagnosis of CF (genotype and sweat test results), 
date of diagnosis of diabetes mellitus, FEV1, date of last hospitalization for pulmonary 
exacerbation and initiation of any systemic steroid therapy. We will collect a list of the 
subject’s current and active medications. Start date and history of CFTR modulator 
therapies. We would also collect data regarding trajectory of weight change since the 
start of highly effective CFTR modulator therapy.  Details of clinical and safety 
outcomes collected at each study visit are listed in table 1. A CGM Dexcom G6 will be 
started for up to 10 days at study visit 1 and the week 8 time point. Patients using their 
own clinical CGM would be allowed to continue using personal CGM. All study 
procedures including CGM, OGTT and labs are being done for research only and not as 
part of clinical care. Participants will be encouraged to schedule follow up with their 
usual diabetes provider within 4-6 weeks after the study conclusion. 
 
Two-hour OGTT Protocol:  
1. Subject will arrive fasting for at least 8 hours except for water.  If subject has not 
been fasting, the study visit must be rescheduled.   

MEDICAL PROTOCOL (HRP-590) 
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2. Subjects are admitted to the clinical research unit.  Finger stick glucose would be 
checked.  Study will be rescheduled if the morning fasting blood glucose is >200 
mg/dl when a participant arrives for the OGTT. 
3. An IV is placed for sequential laboratory draws.  
4. The oral glucose solution (Glucola) at the dose of 1.75 g/kg (max 75 gm) is 
administered at time zero.  
5. Blood will be drawn prior to and at 10, 30, 60, 90, and 120 minutes post glucose 
ingestion for glucose, insulin, c-peptide and glucagon,GLP-1 (active and total) 
and GIP. Samples will be processed, batched and frozen.  
6. Sample for Glucagon, GLP-1 (active and total) and GIP would send to the 
Cytokine Reference Lab at the University of Minnesota for analysis using 
ELISA. Insulin, C-peptide and glucose samples will be sent to the University of 
Minnesota Advanced Research and Diagnostic Laboratory for analysis. 
7. Obtain fingerstick BG on glucometer at 90 and 120 minute time points to 
identify any hypoglycemia. 
▪ 
If blood sugar < 70 mg/dl but > 50 mg/dl and not symptomatic, continue 
research protocol. 
▪ 
If Blood sugar < 70 mg/dl but > 50 mg/dl and symptomatic (feeling 
shaky, hungry, faint, pale) call provider 
▪ 
If Blood sugar < 50 mg/dl, repeat glucometer STAT and if still <50 
mg/dl, call provider and give 4 oz juice. 
8. If the OGTT is stopped early due to hypoglycemia, the next time point of labs 
should be drawn and the patient should be given at least 15 grams of 
carbohydrates until BG is at least 70 mg/dl. 
9. If applicable, patients will be instructed to take the last dose of their usual basal 
insulin dose 24 hours before the OGTT but withhold all rapid-acting insulin 
boluses for at least 8 hours prior to the OGTT.  
10. The second OGTT will be scheduled 2-4 days after the last dose of semaglutide. 
 
 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Visit 0 
Telephon
e 
Pre-
Screening 
Screeni
ng/Visit  
1 
baselin
e  
Visit 2 
 OGTT, 
start 
therapy 
Telephon
e contact  
 
Visit 
3 
 
Telephon
e contact  
Visit 
4 
 
Telephone 
contact  
 
Visit 5 
End of 
study 
Post 
study 
Telephon
e contact 
Time (weeks) 
 
-2 ± 1 
0 
2 ± 1 
4 ± 1 
6 ± 1 
8 ± 1 
10 ± 1 
12 ± 1 
13 ± 1 
Estimated time 
for study visit 
30-60 
min 
60-90 
min 
4-5 hours 
30 min 
60 
min 
30 min 
60 
min 
30 min 
4-5 hours 
30 min 
Assessment of 
inclusion/ 
exclusion criteria  
X 
X[AN] 
 
 
 
 
 
 
 
 
Demography  
Medical history 
X 
X[AN] 
 
 
 
 
 
 
 
 
Concomitant 
medication 
X 
X[AN] 
X 
 
X 
 
X 
 
X 
 
Consent 
 
X 
 
 
 
 
 
 
 
 
Monitoring of  AE 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Blood test (renal 
function, 
electrolytes etc.) 
 
 
X 
 
X 
 
X 
 
X 
 
Review FSBG  
 
 
 
X 
X 
X 
X 
X 
X 
X 
Patient centered 
outcome 
questionnaires 
 
X 
 
 
X 
 
X 
 
X 
X 
PHQ-9 
 
X 
 
 
X 
 
X 
 
X 
 
Vital signs, weight 
 
 
X 
 
X 
 
X 
 
X 
 
OGTT 
 
 
X 
 
 
 
 
 
X 
 
CGM 
 
X 
 
 
 
 
X 
 
 
 
HbA1c 
 
 
X 
 
 
 
 
 
X 
 
Serum Pregnancy 
test 
 
X 
 
 
 
 
 
 
 
 
Urine Pregnancy 
test 
 
 
X 
 
X 
 
X 
 
 
 
Insulin dose 
titration 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
Drug 
accountability 
 
 
 
 
X 
 
X 
 
X 
 
Study drug dose 
titration 
 
 
 
 
X 
 
X 
 
 
 
Table 1. Study visits.  
min, minutes; AE, adverse effects; FSBG, finger stick blood glucose, AN (as needed: medications and medical history may  be reviewed 
at Pre-Screening phone call or at Screening/Visit 1) 
 
Feasibility outcomes:  In this pilot study, we will collect data on important parameters 
that are needed to design a future larger clinical trial to test the hypothesis that weekly 
administration of the long-acting GLP-1RA semaglutide to overweight/obese CFRD 
patients will be safe and well tolerated. Safety will be assessed as the proportion of 
enrolled participants who experience severe adverse events (AE).  Tolerability will be 
evaluated as the proportion (in %) of participants who discontinue their assigned 
treatment due to side effects. We will collect data on consent rate (proportion of all 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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participants who were contacted and eligible who consented), and completion rate 
(proportion of subjects who complete all study visits). If the pilot study demonstrates 
feasibility, then a larger and fully powered trial would be needed to test the hypothesis. 
We will also collect data on adherence to treatment intervention, and on the time needed 
to collect, clean and analyze data. Reasons for not consenting will be collected from 
subjects who decline participation in the study. To monitor for compliance, patients will 
be asked to bring used semaglutide pens at each study visit. Used semaglutide pen will 
be checked for any remaining doses. Participants will be assessed for depression and 
suicidal ideation with the Patient Health Questionnaire-9 (PHQ-9) at the baseline visit 
and   visits 3 ,4 and 5. A participant will be referred to a mental health provider or 
primary care provider if the participant has a PHQ-9 score of ≥10 , any suicidal 
behavior, or any suicidal ideation.  
 
Patient centered outcomes will also be collected as part of feasibility metrics including 
the Gastroparesis Cardinal Symptom Index (GCSI; 9 items) for capturing gastroparesis 
symptoms 21. We will also utilize the Patient Assessment of Gastrointestinal Disorders 
Symptom Severity Index (PAGI-SYM; 20 items) questionnaire that members of the CF 
community have identified as a patient-reported outcome measure that captures the CF 
experience with GI disease 22. We expect to screen 50 participants to recruit 10 
participants. We will consider a consent rate of 20%, a completion rate of 80% as the 
criteria for assessing feasibility. 
5.3 Study Duration:  
This study will be conducted over 24 months. Duration of anticipated 
participation for an individual participant’s would be around 15 weeks (Figure 1). 
Duration anticipated to enroll all study subjects is around 12 months. Duration 
anticipated to complete all study procedures, including any long-term follow-up, 
and data analysis is 24 months. 
5.4 Use of radiation:  
Not applicable 
5.5 Use of Center for Magnetic Resonance Research:  
Not applicable 
6.0 
Data and Specimen Banking 
6.1 Storage and Access:  
Deidentified data will be stored in REDCap or UMN Box for future research use. Only 
the research team will have access to stored data. 
6.2 Data:  
Deidentified data banked for future analyses may include clinical and demographic 
information, lab results, patient-centered outcomes survey responses and treatment data.   
6.3 Release/Sharing:  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Data will be shared with other researchers who request it, under the following conditions: 
• 
Requester provides protocol and IRB approval or Determination of Non-Human 
Participants Research. 
• 
Requester completes Data Use Agreement form as developed by the Health 
Information Privacy and Compliance Office at the University of Minnesota. 
• 
Any data or specimen can be shared but all identifiers will be removed. Requester 
will not be provided with link between identity and study code. 
7.0 
Sharing of Results with Participants 
7.1 If requested results of HbA1C and OGTT will be shared with the participants and 
their CF pulmonary provider. These labs will be shared in-person, via a letter or 
email to the participants and by a letter faxed to CF pulmonary providers. If 
requested, CGM glucose data will be shared with the participants.  
7.2 Sharing of genetic testing:  
N/A 
8.0 
Study Population 
8.1 Inclusion Criteria:  
• Adult subjects 18 years or older with CFRD  
• BMI >26 kg/m2 
• Diagnosis of pancreatic insufficiency (based on treatment with pancreatic 
enzyme replacement therapy)  
• A participant who is capable of becoming pregnant must agree to take 
precautions that are effective in preventing pregnancy throughout this 
study. These methods could include one of the following 1. Complete 
abstinence from sexual intercourse; 2. Oral, injectable, or implanted 
hormonal contraceptives 3. Intrauterine device 4. Tubal ligation 
8.2 Exclusion Criteria:  
• personal or family history of medullary thyroid cancer or multiple 
endocrine neoplasia syndrome type 2 (MEN2) 
• acute pulmonary exacerbation requiring IV antibiotics or systemic 
glucocorticoids within 4 weeks prior to baseline study procedures 
• gastrointestinal(GI) symptom exacerbation defined by current 
nausea/vomiting or diarrhea at the baseline assessment 
• history of chronic GI problems requiring hospitalization in the 1 year prior 
to baseline 
• history of clinically symptomatic pancreatitis 
• history of clinically significant gastroparesis 
• history of eating disorders 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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• less than 24 weeks since start of a new CFTR corrector/modulator therapy 
• pregnancy or lactation 
• severe CF liver disease 
• chronic kidney disease 
• Non-English speakers and those unable to read in English 
• Uncontrolled major depressive disorder (defined as PHQ-9 score of >10) 
• Diagnosis of other severe psychiatric disorders (e.g., schizophrenia, bipolar 
disorder) 
• A Patient Health Questionnaire-9 (PHQ-9) score of ≥10 at screening visit 
• A lifetime history of suicidal attempt 
• Suicidal ideation within the past 1 year before screening visit 
8.3 Pre-Screening and Screening:  
Using a combination of participant self-report and medical record review, 
research staff will confirm each inclusion and exclusion criteria to determine 
eligibility of potential participants who are identified by their treating provider or 
those who respond to recruitment materials. 
Potential participants who respond to recruitment solicitation will be contacted 
by phone. Study staff will provide an overview of the study by following the IRB-
approved phone script. This script includes all required and appropriate 
additional elements of consent disclosure related to the pre-screening process. 
Participants will be asked to provide verbal consent prior to conducting the initial 
phone screen. Participants who consent to proceed with the pre-screening 
process will be documented by study staff. If participants are found to be 
potentially eligible during phone screening, they will be invited to the study for a 
full written consent process in person at their scheduled Screening /Visit 1 that 
covers the remainder of the study, as described in this protocol. If it is 
determined that the patient is not eligible or not interested during the pre-
screening process, any documentation obtained will be securely shredded. During 
the pre-screening process, if the patient reports current suicidal ideation, we will 
offer support and let them know that we will communicate this to their primary 
or CF care team or a mental health provider to provide further evaluation and 
resources. 
As this is a greater than minimal risk study, if there is a question or concern of a 
participant’s capacity to consent, study staff will utilize the MacCAT-CR tool 
solely (instead of the shorter UBACC tool) to exclude patients with diminished 
capacity to consent. 
If there is no concern of a participant’s capacity to consent, we will not utilize the 
MacCAT-CR tool. 
9.0 
Vulnerable Populations 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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9.1 Vulnerable Populations:  
Population / Group 
Identify whether any of the following 
populations will be focus of the 
research (targeted), included, but not 
necessarily the focus or excluded 
from participation in the study. 
Children 
Excluded 
Pregnant women/fetuses/neonates 
Excluded 
Prisoners 
Excluded 
Adults lacking capacity to consent 
and/or adults with diminished capacity 
to consent, including, but not limited 
to, those with acute medical conditions, 
psychiatric disorders, neurologic 
disorders, developmental disorders, 
and behavioral disorders 
Excluded 
Non-English speakers 
Excluded 
Those unable to read (illiterate) 
Excluded 
Employees of the researcher 
Excluded 
Students of the researcher 
Excluded 
Undervalued or disenfranchised social 
group 
 Included but not the focus 
Active members of the military (service 
members), DoD personnel (including 
civilian employees) 
 Included but not the focus 
Individual or group that is approached 
for participation in research during a 
stressful situation such as emergency 
room setting, childbirth (labor), etc. 
Excluded 
Individual or group that is 
disadvantaged in the distribution of 
social goods and services such as 
income, housing, or healthcare. 
 Included but not the focus 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Individual or group with a serious 
health condition for which there are no 
satisfactory standard treatments. 
Primary focus of the research 
Individual or group with a fear of 
negative consequences for not 
participating in the research (e.g. 
institutionalization, deportation, 
disclosure of stigmatizing behavior). 
Excluded 
Any other circumstance/dynamic that 
could increase vulnerability to coercion 
or exploitation that might influence 
consent to research or decision to 
continue in research. 
Excluded 
9.2 Additional Safeguards, if any, to ensure inclusion is appropriate:  
Undervalued/disenfranchised social groups, Active members of the military, and 
Individuals or groups that are disadvantaged in the distribution of social goods and 
services may be included but are not the focus of this study. We will not be 
screening for this so a participant's inclusion in these groups may not be known. 
However, as an additional safeguard, we plan to provide assurance of 
confidentiality, freedom to decline to participate, and the right to withdraw at any 
time without penalty. 
Individuals or groups with a serious health condition for which there are no 
satisfactory standard treatments are the primary focus of this study.  As an 
additional safeguard, participants will be fully informed of the potential risks and 
benefits of the research study. They will also be reminded that their relationship 
with their provider or the UMN will not be affected by their decision whether or 
not to participate in this study. 
If there is a concern or question of a participant’s capacity to consent, study staff 
will utilize MacCAT-CR tool solely (instead of the shorter UBACC tool) to exclude 
patients with diminished capacity to consent. 
If there is no concern of a participant’s capacity to consent, we will not utilize the 
MacCAT-CR tool. 
 
9.3 If research includes potential for direct benefit to participants, provide rationale 
for any exclusions indicated in the table above: 
Safety and efficacy of OZEMPIC® have not been established in pediatric patients 
(younger than 18 years). It is currently approved only in adults with type 2 
diabetes.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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There are limited data with semaglutide use in pregnant women to inform a drug-
associated risk for adverse developmental outcomes. Based on animal 
reproduction studies, there may be potential risks to the fetus from exposure to 
semaglutide during pregnancy. 
10.0 Local Number of Participants 
10.1 Local Number of Participants to be Consented:  
Up to 15 participants will be consented to account for replacement of drop-outs 
11.0 Local Recruitment Methods 
11.1 Recruitment Process:  
Participants will be recruited from UMN CF center. Recruitment related text will 
be send to UMN Cystic Fibrosis Center email listserv to assist with recruiting 
subjects with cystic fibrosis. Only CF Center patients who opt in to the listserv will 
receive these communications.  They may unsubscribe at any time. Patients who 
opt in to the listserv sign a form when providing their email address.  They are 
opting in to receive any news sent out through the listserv, which may include 
research study opportunities. 
Potential participants will be identified using clinic records and letters will be sent 
to potential participants by their provider, including study investigators. Clinics 
include the CF clinics, Endocrine clinics, or Pulmonary clinics; all located at the 
Clinics and Surgery Center.  
The IRB-approved Minnesota CF Center database/CFF Patient Registry (IRB# 
7405M00054) will be queried for subjects who meet study inclusion and exclusion 
criteria.  Patients who are followed at the Center sign consent for the use of their 
clinical data for research and are aware of the possibility of being contacted for 
research participation. The potential subjects are followed at our CF Center. 
Subjects identified through database query will be contacted by the research 
coordinators or the investigators. Contact will be made either at the time of a 
routine clinic visit, email or by phone. Those who have opted out of research will 
not be contacted. 
In addition, study information including contact information will be posted within 
ClincalTrials.gov and Study Finder. 
11.2 Identification of Potential Participants:  
Participants could self-identify in response to UMN Cystic Fibrosis Center email 
listserv and contact the research staff; at that point, research staff will verbally 
confirm basic eligibility.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Research staff will review Fairview medical record for opt-out status for patients 
identified using medical records who are then sent recruitment letters. The 
recipients of the recruitment letter will be the PI’s patients.  
Research staff will also supplement as needed self-identifier recruitment by 
reviewing medical records of affiliated study clinicians. Providers who have a 
treating relationship with the patient may discuss research opportunities during a 
clinical encounter regardless of research opt-out status. 
11.3 Recruitment Materials:  
• CF listserv email text 
• Recruitment Letter 
11.4 Payment: 
Participants will be compensated at the completion of study visits 2, 3, 4, 5 at the following 
rates for a total of $600:  
− Visit 2: $100 
− Visit 3: $100 
− Visit 4: $100 
− Visit 5: $100 
− Study Completion: $200 
Compensation will be issued using the ClinCard debit card program or by check issued 
by the University of Minnesota and sent to the participant’s home address. 
Participants will be reimbursed for travel expenses for onsite study visits including 
mileage, as per standard federal rates for reimbursement. 
12.0 Withdrawal of Participants 
12.1 Withdrawal Circumstances:  
Participants will be withdrawn without their consent if at any point following 
enrollment they develop any of the exclusion criteria. 
Participants will be withdrawn and stopped from study drug, if they experience 
serious adverse events related to study drug or procedure, recurrent severe 
hypoglycemia, suicidal ideation or development of  depression PHQ > 10, 
pregnancy or at the discretion of the DSMB.  
Participants are free to withdraw from participation in the study at any time. 
12.2 Withdrawal Procedures:  
No additional data will be collected from a participant who withdraws from the 
study. 
If a participant wishes to withdraw or we determine that the participant should 
withdraw, we will terminate data collection and discuss with the participant the 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Template Revised On: 10/28/2022 
reasons for withdrawal. All data collected up to that point will be used in analysis 
unless the participant wishes for their data not to be used. 
12.3 Termination Procedures:  
This study may be temporarily suspended or prematurely terminated if there is 
sufficient reasonable cause. Written notification, documenting the reason for 
study suspension or termination, will be provided by the suspending or 
terminating party to the investigator, funding agency, IND/IDE sponsor, and 
regulatory authorities, as appropriate. If the study is prematurely terminated or 
suspended, the PI will promptly inform the IRB and will provide the reason(s) for 
the termination or suspension. The study team will notify the participants of the 
study termination. 
13.0 Risks to Participants 
13.1 Foreseeable Risks:  
Hypoglycemia related to OGTT: The OGTT is a routine clinical procedure which 
patients with CF undergo on an annual basis for CFRD screening.  Reactive 
hypoglycemia can occur during OGTT.  Fingerstick BG will be obtained on 
glucometer at 90 and 120 minute time points to identify any hypoglycemia. OGTT 
will be stopped if BG goes < 50 mg/dl 
IV Risks: There may be pain involved with the IV placement.  There is a small risk 
of bleeding under the skin that will produce a bruise.  An infection is extremely 
rare with the placement of the IV for frequent sampling. 
CGM Skin Reactions: The CGM sensor may produce pain when it is inserted into 
the skin.  There is a low risk for developing a local skin infection at the site of the 
sensor needle placement.  Itchiness, redness, bleeding and bruising at the 
insertion site may occur as well as local tape allergies. 
Risk of fasting: Since the study participants will present fasting to one of the study 
sessions, some participants may experience hunger, irritability, fidgetiness, 
and/or lack of cooperation or attention. Furthermore, mild headaches, shakiness 
and/or dizziness may be experienced secondary to the fasting requirement. 
Risks of questionnaires: The questionnaires will assess personal details such as 
information about treatment satisfaction, health status and symptoms, and diet 
history. These questions may bring to mind uncomfortable thoughts, emotions or 
memories. Some participants may face fatigue, embarrassment, frustration, or 
other challenges while completing these questionnaires. To mitigate this risk, 
participants will be reminded that participation in the study is voluntary and as 
such, they may skip individual questions or the questionnaire entirely.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Side effects related to Semaglutide: The most common adverse reactions, 
reported with Ozempic® (semaglutide) are nausea, vomiting, diarrhea, abdominal 
pain, and constipation. 
Common AE table taken from Ozempic® (semaglutide) prescribing information is 
copied below (https://www.ozempic.com/prescribing-information.html, 
 
We will use a checklist of AE reported in the Ozempic® prescribing information to 
monitor for side effects at all study visits. Hypoglycemic events will be captured 
using the American Diabetes Association definitions. 
Other Adverse Reactions per Ozempic® (semaglutide) prescribing information are 
listed below.  
i. Hypoglycemia: Insulin induced hypoglycemia--- semaglutide may reduce 
insulin requirements, which would become evident as subjects would 
experience more hypoglycemia. 
Insulin dose will be titrated to avoid hypoglycemia. 
Participants will be educated on the signs and symptoms of 
hypoglycemia. They will also be provided with an information sheet 
containing instructions for how and when to seek medical care and 
notify the study staff in the event of any hypoglycemia or other adverse 
events. 
ii. Injection Site Reactions: In placebo-controlled trials, injection site 
reactions (e.g., injection-site discomfort, erythema) were reported in 
0.2% of OZEMPIC®-treated patients.  
iii. Increases in Amylase and Lipase: In placebo-controlled trials, patients 
exposed to OZEMPIC® had a mean increase from baseline in amylase of 
13% and lipase of 22%. These changes were not observed in placebo-
treated patients.  

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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We are recruiting patients with CF who are pancreatic insufficient and 
are likely not at risk of acute pancreatitis because of very little remaining 
exocrine tissue. We will monitor lipase level at baseline and week 12. 
iv. Pancreatitis: In glycemic control trials, acute pancreatitis was confirmed 
by adjudication in 7 OZEMPIC®-treated patients (0.3 cases per 100 
patient years) versus 3 in comparator-treated patients (0.2 cases per 100 
patient years). One case of chronic pancreatitis was confirmed in an 
OZEMPIC®-treated patient. In a 2-year trial, acute pancreatitis was 
confirmed by adjudication in 8 OZEMPIC®-treated patients (0.27 cases 
per 100 patient years) and 10 placebo-treated patients (0.33 cases per 
100 patient years), both on a background of standard of care. 
We are recruiting patients with CF who are pancreatic insufficient and 
are likely not at risk of acute pancreatitis because of very little remaining 
exocrine tissue. We will monitor lipase level at baseline and week 12. 
v. Cholelithiasis: In placebo-controlled trials, cholelithiasis was reported in 
1.5% and 0.4% of patients-treated with OZEMPIC® 0.5 mg and 1 mg, 
respectively. Cholelithiasis was not reported in placebo-treated patients. 
vi. Increases in Heart Rate In placebo-controlled trials, OZEMPIC® 0.5 mg 
and 1 mg resulted in a mean increase in heart rate of 2 to 3 beats per 
minute. There was a mean decrease in heart rate of 0.3 beats per 
minute in placebo-treated patients. 
Heart rate and blood pressure will be monitored at each study visit.  
vii. Fatigue, Dysgeusia and Dizziness Other adverse reactions with a 
frequency of >0.4% were associated with OZEMPIC® include fatigue, 
dysgeusia and dizziness. 
viii. Hypersensitivity Reactions: Serious hypersensitivity reactions (e.g., 
anaphylaxis and angioedema) have been reported. 
ix. Risk of Thyroid C-cell Tumors: In mice and rats, semaglutide caused a 
dose-dependent and treatment-duration-dependent increase in the 
incidence of thyroid C-cell tumors (adenomas and carcinomas) after 
lifetime exposure at clinically relevant plasma exposures [see Nonclinical 
Toxicology. It is unknown whether OZEMPIC® causes thyroid C-cell 
tumors, including medullary thyroid carcinoma (MTC), in humans as 
human relevance of semaglutide-induced rodent thyroid C-cell tumors 
has not been determined. 
x. Diabetic Retinopathy Complications: In a 2-year trial involving patients 
with type 2 diabetes and high cardiovascular risk, more events of 
diabetic retinopathy complications occurred in patients treated with 
OZEMPIC® (3.0%) compared to placebo (1.8%). The absolute risk 

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increase for diabetic retinopathy complications was larger among 
patients with a history of diabetic retinopathy at baseline (OZEMPIC® 
8.2%, placebo 5.2%) than among patients without a known history of 
diabetic retinopathy (OZEMPIC® 0.7%, placebo 0.4%). 
xi. Acute Kidney Injury: There have been postmarketing reports of acute 
kidney injury and worsening of chronic renal failure, which may 
sometimes require hemodialysis, in patients treated with GLP-1 receptor 
agonists. Some of these events have been reported in patients without 
known underlying renal disease. A majority of the reported events 
occurred in patients who had experienced nausea, vomiting, diarrhea, or 
dehydration. Excessive weight loss: Excessive weight loss leading to BMI 
going below the minimum goal threshold of 22 in women and 23 in men 
with cystic fibrosis, could be a potential concern. 
We are recruiting subjects > BMI of 26 and so risk of BMI going below 
this threshold over 3 months therapy is unlikely. Should this occur the 
semaglutide dose will be reduced or discontinued. 
Suicidal behavior and ideation have been reported in clinical trials with other 
weight management products. Semaglutide under the brand name WEGOVY® is 
approved for chronic weight management. WEGOVY® prescribing information 
recommends avoiding WEGOVY® (semaglutide) in patients with a history of 
suicidal attempts or active suicidal ideation. WEGOVY® will not be used in the 
current study.  
General participation risks: There is always the risk of a loss of confidentiality in 
any study. Participant identifiable information will be stored securely to 
minimize this risk. 
13.2 Reproduction Risks:  
Pregnant women will not be eligible for participation. 
13.3 Risks to Others:  
Not applicable. No risk to others. 
14.0 Potential Benefits to Participants 
14.1 Potential Benefits: 
Treatment with Semaglutide may result in improvement glucose control and 
weight loss, however these benefits cannot be guaranteed. 
15.0 Statistical Considerations 
15.1 Data Analysis Plan:  

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The primary outcomes are related to feasibility, including safety and treatment 
tolerability. Safety will be evaluated as the proportion (in %) of participants who 
experience a serious adverse event during the study. Tolerability will be evaluated 
as the proportion (in %) of participants who discontinue their assigned treatment 
due to side effects. A 95% exact confidence interval will also be calculated for the 
primary outcomes. Secondary outcomes will be change in glucose and insulin area 
under the curve during the OGTT and the time to peak insulin level. Additional 
secondary outcome measures include time in range, glycemic variability and time 
below range based on CGM,  HbA1c,  moderate/mild adverse events and if 
applicable insulin dose (IU/day for both bolus and basal). An exploratory analysis 
will be done to examine any potential impact of baseline β cell function as 
measured by OGTT based outcomes on the response and side effects to the study 
drug.   
Safety will be assessed as the proportion of enrolled participants who experience 
severe adverse events (AE).  Tolerability will be evaluated as the proportion (in %) 
of participants who discontinue their assigned treatment due to side effects. We 
will collect data on consent rate (proportion of all participants who were 
contacted and eligible who consented), and completion rate (proportion of 
subjects who complete all study visits). 
We will also collect data on adherence to treatment intervention, and on the time 
needed to collect, clean and analyze data. Reasons for not consenting will be 
collected from subjects who decline participation in the study. 
We will consider a consent rate of 20%, a completion rate of 80% as the criteria 
for assessing feasibility. 
Study data will be collected using REDCap (https://www.ctsi.umn.edu/researcher-
resources/tools-and-software/redcap). Data analysis will be carried out using SAS 
software version 9.4 (SAS Institute Inc., Cary, NC). 
15.2 Power Analysis:  
10 adult subjects with CF will be recruited. This sample size was chosen based on 
feasibility considerations. This is a pilot study and is not fully powered to 
demonstrate efficacy. This study will provide preliminary data (estimates of 
serious AE rate, tolerance, and effect sizes as well as of its variance) for a future 
larger placebo-controlled clinical trial. 
15.3 Statistical Analysis:  
 Demographics and baseline characteristics of enrolled participants will be 
summarized using descriptive statistics. Mean, median, standard deviation, inter-
quartile range, and range will be calculated for continuous outcomes at each time 
points as well as their changes compared to the baseline. Boxplots and trajectory 
curves will be plotted to display the distributions and longitudinal changes of the 

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variables. Paired t test or Wilcoxon signed-rank test (a nonparametric test) will be 
used to compare baseline with the final time point measures. Missing data will be 
excluded from analysis (when evaluating change from pre to post, participants 
with missing data at either pre or post will be excluded). The analyses will be 
done on an intention-to-treat basis, which will consist of all patients who receive 
at least one dose of study drug (once a patient is enrolled, he/she will be included 
in analysis, unless there is missing data for pre-post change); regardless of 
whether he/she completed the treatment). 
15.4 Data Integrity:  
The PI will periodically review data for completeness and to ensure that all 
procedures are being followed as detailed in the protocol.  The assigned 
Regulatory Specialist will also perform periodic quality assurance monitoring at 
any point requested by the PI. 
16.0 Health Information and Privacy Compliance 
16.1 
Select which of the following is applicable to your research: 
☐ My research does not require access to individual health information and 
therefore assert HIPAA does not apply.   
 
x I am requesting that all research participants sign a HIPCO approved HIPAA 
Disclosure Authorization to participate in the research (either the standalone 
form or the combined consent and HIPAA Authorization). 
☐ I am requesting the IRB to approve a Waiver or an alteration of research 
participant authorization to participate in the research. 
Appropriate Use for Research:  
☐ An external IRB (e.g. Advarra) is reviewing and we are requesting use of the 
authorization language embedded in the template consent form in lieu of the 
U of M stand-alone HIPAA Authorization.  Note: External IRB must be serving 
as the privacy board for this option. 
 
16.2 
Identify the source of Private Health Information you will be using for your 
research (Check all that apply)   
☐ I will use the Informatics Consulting Services (ICS) available through CTSI 
(also referred to as the University's Information Exchange (IE) or data 
shelter) to pull records for me 
x I will collect information directly from research participants. 

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☐ I will use University services to access and retrieve records from the Bone 
Marrow Transplant (BMPT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) database. 
x I will pull records directly from EPIC. 
☐ I will retrieve record directly from axiUm / MiPACS 
☐ I will receive data from the Center for Medicare/Medicaid Services  
☐ I will receive a limited data set from another institution  
☐ Other.  Describe: 
16.3 
Explain how you will ensure that only records of patients who have agreed to 
have their information used for research will be reviewed. 
During the pre-screening process, only those patients who have not opted out 
of having their records used for research will be screened. However, providers 
who have a treating relationship with the patient may discuss research 
opportunities during a clinical encounter regardless of research opt-out status 
and opt-out status will not matter if a participant contacts us first. 
16.4 
Approximate number of records required for review: 
We anticipate reviewing 50 records in order to meet our required sample size.  
16.5 
Please describe how you will communicate with research participants during 
the course of this research.  Check all applicable boxes 
☐ This research involves record review only. There will be no communication 
with research participants. 
☐ Communication with research participants will take place in the course of 
treatment, through MyChart, or other similar forms of communication used 
with patients receiving treatment.  
x Communication with research participants will take place outside of 
treatment settings. If this box is selected, please describe the type of 
communication and how it will be received by participants. 
 We may communicate with participants via: 
     - Telephone (using a study-specific phone number); 
     - Text message if participants agree that we may communicate with them by 
text message by signing the Unsecured Email Authorization Form and/or 
UMN Text Guidelines and Consent for Text Message Correspondence For 
Research Participants Form, if they have not signed previously.; 
     - Unsecure email if the participants agree that we may communicate with 
them through unsecured emails by signing the Unsecured Email 
Authorization Form, if they have not signed previously. 

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16.6 
Explain how the research team has legitimate access to patients/potential 
participants: 
Patients come from the Study Investigator’s patient population and/or are 
followed at the MN CF Center. 
The research team will be permitted to access sources of private information 
once enrolled because all participants will be required to sign a HIPAA waiver 
at the time of informed consent. 
16.7 Location(s) of storage, sharing and analysis of research data, including any links to 
research data (check all that apply).   
☐ In the data shelter of the Information Exchange (IE)  
 ☐ Store 
☐ Analyze 
☐ Share 
☐ In the Bone Marrow Transplant (BMT) database, also known as the HSCT 
(Hematopoietic Stem Cell Transplant) Database  
 ☐ Store 
☐ Analyze 
☐ Share 
x In REDCap (recap.ahc.umn.edu)  
 x Store  
x Analyze 
x Share 
☐ In Qualtrics (qualtrics.umn.edu) 
 ☐ Store 
☐ Analyze 
☐ Share 
x In OnCore (oncore.umn.edu)  
 x Store  
☐ Analyze 
☐ Share 
x In the University’s Box Secure Storage (box.umn.edu) 
 x Store  
xAnalyze 
x Share 
x In an AHC-IS supported server. Provide folder path, location of server and IT 
Support Contact: 
MedDerm (\\med.ahc.umn.edu\med) (N:) 
 x Store  
☐ Analyze 
☐ Share 
☐ In an AHC-IS supported desktop or laptop.  
Provide UMN device numbers of all devices:  
 ☐ Store 
☐ Analyze 
☐ Share 
☐ Other. Describe:  
Indicate if  data will be collected, downloaded, accessed, shared or stored using a 
server, desktop, laptop, external drive or mobile device (including a tablet 

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computer such as an iPad or a smartform (iPhone or Android devices) that you 
have not already identified in the preceding questions 
☐I will use a server not previously listed to collect/download research data 
☐I will use a desktop or laptop not previously listed 
☐I will use an external hard drive or USB drive (“flash” or “thumb” drives) not 
previously listed  
☐I will use a mobile device such as an tablet or smartphone not previously listed 
16.8 Consultants. Vendors. Third Parties.  
N/A 
16.9 
Links to identifiable data:  
All data will be labeled with an identification code unique to the participant. 
Study staff will keep the mapping of this identification code to the identity of 
the participant separately from the data in REDCap, UMN Box, or an HST-IS 
supported server. Any internal data reports will use only these codes and will 
not use any identifiable information. Any external data reports, abstracts, 
publications, presentations, etc. will present de-identified, grouped, and/or 
aggregate data. Any reports to the University of Minnesota IRB (such as Adverse 
Event reporting and annual renewal reports) will be kept confidential; they will 
not include participant- identifiable information; only the participant’s 
identification code will be used. 
16.10 Sharing of Data with Research Team Members.  
Only IRB-approved members of the study team will have access to the data. 
Data will be shared through the medical record, OnCore, REDCap, HST-IS secure 
server, or UMN Box. 
16.11 Storage of Documents:  
Paper documents will be stored in a locked cabinet in a locked research office 
only accessible to research staff. Electronic documents will be stored in REDCap, 
UMN Box, and an HST-IS supported server. 
16.12 Disposal of Documents:  
We will retain research documents for a period of 2 years following the date a 
marketing application is approved for the drug for the indication for which it is 
being investigated; or, if no application is to be filed or if the application is not 
approved for such indication, until 2 years after the investigation is 
discontinued and FDA is notified. HIPAA forms will be retained for 6 years.  
If the records are moved offsite during or after this time period, they will be 
housed in the Academic Health Center Storage Facility at the following address: 

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Reuse/AHC Warehouse 883 29th Ave SE Minneapolis, MN 55414.  Records are 
retrievable at any time once they are moved to this storage facility. 
We will then dispose of paper documents in a secure UMN 
shredding/document destruction box. All electronic documents will be archived 
in the HST-IS supported server. 
17.0 Confidentiality 
17.1 Data Security:  
All standard confidentiality procedures will be observed for this study and all 
research staff will be trained before they will be allowed contact with participants 
or data. 
All University of Minnesota confidentiality and privacy policies and procedures 
will be followed by all research staff. 
CRF data for this study will be entered into a REDCap database, which uses a 
MySQL database via a secure web interface with data checks used during data 
entry to ensure data quality. REDCap includes a complete suite of features to 
support HIPAA compliance, including a full audit trail, user-based privileges, and 
integration with the institutional LDAP server. The MySQL database and the web 
server are housed on secure servers operated by the University of Minnesota 
Academic Health Center’s Information Systems group (AHC-IS). The servers are in 
a physically secure location on campus and are backed up nightly, with the 
backups stored in accordance with the AHC-IS retention schedule of daily, weekly, 
and monthly tapes retained for 1 month, 3 months, and 6 months, respectively. 
Weekly backup tapes are stored offsite. The AHC-IS servers provide a stable, 
secure, well-maintained, and high-capacity data storage environment, and both 
REDCap and MySQL are widely used, powerful, reliable, well-supported systems. 
Access to the study's data in REDCap will be restricted to the members of the 
study team by username and password. 
REDCap™ files will be exported to shared drives housed under HIPAA-compliant 
AHCIS servers on the MedDerm (\\med.ahc.umn.edu\med)(N:) shared drive or 
UMN Box. Any other identifiable electronic data, including logs, will also be 
password-protected and stored on this HIPAA-compliant server and UMN Box. 
Only study members will have access to the MedDerm folder/server and UMN 
Box.  All paper data, source or CRF or otherwise, will be kept in locked cabinets in 
locked research offices. 
In order to certify study data entered into REDCap, completed REDCap data 
collection forms will be printed, reviewed and verified (by signing and dating) as 
final by the PI or a designated member of the study team. Upon review and 
verification, the data on these forms will serve as the final study data. 
Consent documents will not be placed in the participant’s medical record. 

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Vitals, height/weight and CGM will not be entered in the participants' medical 
records. 
17.2 Data Sharing: 
Prior to sharing any study data, all personal identifiers will be removed from the 
dataset and replaced with participants’ unique study identifier. The link 
associating participants with their study identifier will not be shared with outside 
researchers. Data will only be shared with other researchers after they have 
provided the study protocol and IRB approval (or Determination of Non-Human 
Participants Research), and completed a Data Use Agreement form with the 
Health Information Privacy and Compliance Office at the University of Minnesota. 
18.0 Provisions to Monitor the Data to Ensure the Safety of Participants 
18.1 Data Integrity Monitoring.  
While there will be no planned interim data analysis, the PI will periodically 
review data for completeness and to ensure that all procedures are being 
followed as detailed in the protocol.  
The study will be monitored twice yearly in accordance with CTSI monitoring 
policies. 
The study will permit trial-related monitoring, audit, IRB review, and regulatory 
inspection, providing direct access to source data/documents. 
18.2 Data Safety Monitoring.  
It will be the responsibility of the Principal Investigator to oversee the safety of 
the study. The PI will review cumulative raw data, trends in AEs, SAEs and 
UPIRTSO on an ongoing basis. Safety data will be captured in the CRFs for each 
visit. Any safety event meeting the IRB’s urgent reporting criteria will be reported 
to the IRB within its published timelines.  
In addition to the PI’s responsibility for oversight, a data and safety monitoring 
board (DSMB) will be established, which will include at least one  obesity 
medicine specialist or endocrinologist, and one biostatistician. DSMB members 
will not be affiliated with the study. The DSMB will meet regularly (frequency to 
be determined by DSMB members but no less than every six months) during the 
study to review data and evaluate participant safety.  
A charter for the DSMB will be developed and approved by its members along 
with a plan for frequency of data review prior to the commencement of the 
study. Review materials for the DSMB will be prepared and presented by the 
study biostatistician. A report from each meeting will be sent to the PI and co-
investigators advising on the continuation of the study and any suggestions for 
trial improvement. This report will also be sent to the IRB. Important charges of 
the DSMB will be to closely monitor progress and timelines related to recruitment 

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goals, fidelity to the protocol (e.g. regularly review the number and types of 
protocol deviations), and to closely monitor the quality and integrity of the data. 
The DSMB will communicate any concerns relevant to these issues of study 
conduct to the PI and note specific recommendations for improvement in 
meeting reports. 
Adverse Event (AE) vs. Serious Adverse Event (SAE): An adverse event is any 
undesirable experience associated with the use of a medical product in a 
participant. A serious adverse event (SAE) will immediately be reported to the 
FDA when the participant outcome is: 
• 
Death: Report if you suspect that the death was an outcome of the 
adverse event, and include the date if known.  
• 
Life-threatening: Report if suspected that the patient was at substantial 
risk of dying at the time of the adverse event, or use or continued use of 
the device or other medical product might have resulted in the death of 
the patient. 
• 
Hospitalization (initial or prolonged): Report if admission to the hospital 
or prolongation of hospitalization was a result of the adverse event. 
Emergency room visits that do not result in admission to the hospital 
should be evaluated for one of the other serious outcomes (e.g., life-
threatening; required intervention to prevent permanent impairment or 
damage; other serious medically important event). 
• 
Disability or Permanent Damage: Report if the adverse event resulted in a 
substantial disruption of a person's ability to conduct normal life 
functions, i.e., the adverse event resulted in a significant, persistent or 
permanent change, impairment, damage or disruption in the patient's 
body function/structure, physical activities and/or quality of life. 
• 
Congenital Anomaly/Birth Defect: Report if you suspect that exposure to 
a medical product prior to conception or during pregnancy may have 
resulted in an adverse outcome in the child. 
• 
Required Intervention to Prevent Permanent Impairment or Damage 
(Devices): Report if you believe that medical or surgical intervention was 
necessary to preclude permanent impairment of a body function, or 
prevent permanent damage to a body structure, either situation 
suspected to be due to the use of a medical product. 
• 
Other Serious (Important Medical Events): Report when the event does 
not fit the other outcomes, but the event may jeopardize the patient and 
may require medical or surgical intervention (treatment) to prevent one of 
the other outcomes. Examples include allergic bronchospasm (a serious 
problem with breathing) requiring treatment in an emergency room, 
serious blood dyscrasias (blood disorders) or seizures/convulsions that do 
not result in hospitalization. The development of drug dependence or drug 
abuse would also be examples of important medical events. 

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Severity of an adverse event: The following guidelines will be used to describe 
severity of an adverse event. 
• 
Mild: Events require minimal or no treatment and do not interfere with 
the participant’s daily activities.  
• 
Moderate: Events result in a low level of inconvenience or concern with 
the therapeutic measures. Moderate events may cause some interference 
with functioning. 
• 
Severe: Events interrupt a participant’s usual daily activity and may 
require systemic drug therapy or other treatment. Severe events are 
usually potentially life-threatening or incapacitating.  Of note, the term 
“severe” does not necessarily equate to “serious”. 
Relationship to study intervention: The following guidelines will be used to 
describe the “relatedness” of an adverse event. 
• 
Related: The AE is known to occur with the study intervention, there is a 
reasonable possibility that the study intervention caused the AE, or there 
is a temporal relationship between the study intervention and event. 
Reasonable possibility means that there is evidence to suggest a causal 
relationship between the study intervention and the AE. 
• 
Not Related: There is not a reasonable possibility that the administration 
of the study intervention caused the event, there is no temporal 
relationship between the study intervention and event onset, or an 
alternate etiology has been established. 
Expectedness: The Investigator will be responsible for determining whether an 
adverse event is expected or unexpected. An adverse event will be considered 
unexpected if the nature, severity, or frequency of the event is not consistent 
with the risk information previously described for the study intervention. 
Reporting of adverse events: Information on all adverse events will be collected 
including the: 
• 
Event description 
• 
Time of onset 
• 
Assessment of severity 
• 
Relationship to study intervention 
• 
expectedness 
• 
Time of resolution/stabilization of the event  
All adverse events occurring while on study will be documented appropriately 
regardless of relationship. All adverse events will be followed to adequate 
resolution. 
Any medical condition that is present at the time that the participant is screened 
will be considered as baseline and not reported as an adverse event. However, if 

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the participant’s condition deteriorates at any time during the study, it will be 
recorded as an adverse event.  
The investigator will record all reportable events with start dates occurring any 
time after informed consent is obtained until 7 (for non-serious adverse events) 
or 30 days (for serious adverse events) after the last day of study participation.  At 
each study visit, the investigator will inquire about the occurrence of the adverse 
event since the last visit. 
19.0 Provisions to Protect the Privacy Interests of Participants 
19.1 Protecting Privacy:  
Participants will sign a consent form and a HIPAA Authorization which will detail 
what data and under what circumstances will be shared with research staff and 
non-research staff.  
It is not anticipated that any survey will ask intrusive or difficult questions. 
However, surveys will be explained in full detail in the consent so that participants 
can make informed decisions before they enroll.  
The consent will also detail under which conditions any information may be shared 
with those outside of the internal research staff. 
Confidentiality of the research participants will be maintained. All data will be 
stored in locked offices and will not be released without consent of participants. 
Data to be used in scientific presentations or publications will not contain 
participant identifiers. 
All material will be used exclusively for research. Pre-existing chart (electronic 
medical record) information may also be used. Data obtained will be stored in a 
confidential database. The principal investigator and designated study staff will 
have access to the linkages, which will be stored in a separate, secured location. 
Hard copies of data, including source documents with identifiers, will be kept in 
locked file cabinets in a locked office until the completion and publication of the 
study, at which time any identifiers will be removed and data will be stored at a 
secure storage facility for 7 years. Access to the locked file cabinet will be given to 
the study coordinators and principal investigator only. 
19.2 Access to Participants:  
Participants will sign a consent and HIPAA authorization. 
Some of the participants, but not all, will be patients of the Fairview system and 
some will be patients of the PI.  Accessing their medical records with their 
permission will make it easier for them to participate in the study so that we can 
verify their diagnoses without asking them to find and share copies of their 
medical records in order to qualify for the study.  If they do not wish for the study 
to access their medical records directly, they may also share the components of 
their medical records that support their diagnosis. 

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20.0 Compensation for Research-Related Injury 
20.1 Compensation for Research-Related Injury:  
In the event that this research activity results in an injury, treatment will be 
available, including first aid, emergency treatment and follow-up care as needed. 
Care for such injuries will be billed in the ordinary manner to the subject or their 
insurance company 
20.2 Contract Language: 
Not applicable. No contract. 
21.0 Consent Process 
21.1 Consent Process (when consent will be obtained): 
At the start of the study, informed consent will be obtained by the research 
coordinator or PI in person. All consent procedures will take place remotely or at 
the CSC or clinical research unit (CRU) in a private room. The entire consent 
document will be verbally explained to eligible participants, including all study 
procedures and expectations, risks, benefits, and what volunteering means. 
Candidates will be given time to read the consent before their scheduled 
Screening/Visit 1, ask questions, and have as much time needed to review. The 
study team will ask the participant questions about the informed consent form to 
assess comprehension. If the study team feels the participant understands what’s 
being asked of them, the participant and study team will sign the informed 
consent form. This will be done prior to any procedures being conducted. The 
participants may withdraw consent at any time throughout the course of the 
study. Photocopy of signed ICF/HIPAA will be provided to the participant. 
Throughout the study, specific risks and procedures will be reviewed to ensure 
continued voluntary and informed consent. 
21.2 Waiver or Alteration of Consent Process (when consent will not be obtained):  
Not applicable. No waiver or alteration of consent will be requested or used. 
21.3 Waiver of Written/Signed Documentation of Consent (when written/signed 
consent will not be obtained):  
We are requesting a waiver of written/signed documentation of consent for the 
pre-screening portion of this study. A short phone script will be read to the 
participant before any pre-screening questions are asked. The participant will 
need to provide verbal consent to answering these pre-screening questions 
before proceeding. This waiver will not adversely affect the rights and welfare of 
the participants. Their clinical care with the CF care team and with M Health 
Fairview will not be affected adversely by their pre-screening responses.  
Furthermore, we will obtain written consent at the Screening/Visit 1 in person. 

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21.4 Non-English Speaking Participants:  
Not applicable. No non-English speaking participants will be enrolled. 
21.5 Participants Who Are Not Yet Adults (infants, children, teenagers under 18 years 
of age): 
Not applicable. No individual under the age of 18 will be enrolled. 
21.6 Cognitively Impaired Adults, or adults with fluctuating or diminished capacity to 
consent: 
Not applicable. No adult with cognitive impairment or with fluctuating or 
diminished capacity will be enrolled. The PI and study staff with consent 
delegation have completed necessary Capacity to Consent trainings and will be 
available for assessments as necessary and appropriate using the MacCAT-CR 
process solely (not the shorter UBACC tool). 
21.7 Adults Unable to Consent: 
Not applicable. All individuals will be able to consent for themselves. 
22.0 Setting 
22.1 Research Sites:  
All participant-facing procedures including consent will take place remotely, at 
CSC, or clinical research unit (CRU). Non-participant involved activities will take 
place in coordinator and staff offices. 
22.2 International Research:  
Not applicable  
23.0 Multi-Site Research 
Not applicable. Single site only. 
24.0 Coordinating Center Research 
Not applicable 
25.0 Resources Available 
25.1 Resources Available:  
The CF center at the University of Minnesota cares for about 540 patients 
including 400 adults and 140 children (excluding transplant patients). These data 
indicate that we have the eligible patient to recruit successfully for this pilot 
study. 
We have an established research team at the MN CF Center. Our research team 
has adequate space and equipment to perform the research procedures. 

MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
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Participants will be referred to an endocrinologist or their personal physician for 
any medical or psychological evaluation that may be required as a result of the 
research. We have a dedicated CF Center clinical team. The care and well-being of 
our patients is priority over research. If the patient needs medical care due to a 
consequence of the research study, it will be provided to them. 
26.0 References 
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Stephenson AL, Mannik LA, Walsh S, et al. Longitudinal trends in nutritional status and 
the relation between lung function and BMI in cystic fibrosis: a population-based cohort study. 
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5. 
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Annual Data Report https://www.cff.org/Research/Researcher-Resources/Patient-
Registry/2019-Patient-Registry-Annual-Data-Report.pdf2019. 
6. 
Harindhanavudhi T, Wang Q, Dunitz J, Moran A, Moheet A. Prevalence and factors 
associated with overweight and obesity in adults with cystic fibrosis: A single-center analysis. J 
Cyst Fibros. 01 2020;19(1):139-145. doi:10.1016/j.jcf.2019.10.004 
7. 
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Anthropometric Parameters in Individuals with Cystic Fibrosis: An Evidence Analysis Center 
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8. 
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Associated with Weight Gain and Improvement in FEV1 in People with Cystic 
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Holst JJ. The physiology of glucagon-like peptide 1. Review. Physiol Rev. Oct 
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semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric 
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postprandial glycemia in cystic fibrosis--effects of pancreatic enzyme supplementation. J Clin 
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Perano SJ, Couper JJ, Horowitz M, et al. Pancreatic enzyme supplementation improves 
the incretin hormone response and attenuates postprandial glycemia in adolescents with cystic 
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MEDICAL PROTOCOL (HRP-590) 
PROTOCOL TITLE: Efficacy and safety of GLP-1 agonist therapy in overweight and obese 
subjects with cystic fibrosis-related diabetes: a pilot study  
VERSION DATE: 8/9/2024 
 
Page 40 of 40 
Template Revised On: 10/28/2022 
13. 
Geyer MC, Sullivan T, Tai A, et al. Exenatide corrects postprandial hyperglycaemia in 
young people with cystic fibrosis and impaired glucose tolerance: A randomized crossover trial. 
Diabetes Obes Metab. 03 2019;21(3):700-704. doi:10.1111/dom.13544 
14. 
Kelly A, Sheikh S, Stefanovski D, et al. Randomized, Controlled Trial Of Sitagliptin 
And Islet Function In Cystic Fibrosis With Abnormal Glucose Tolerance. J Clin Endocrinol 
Metab. May 22 2021;doi:10.1210/clinem/dgab365 
15. 
Moran A, Brunzell C, Cohen RC, et al. Clinical care guidelines for cystic fibrosis-
related diabetes: a position statement of the American Diabetes Association and a clinical 
practice guideline of the Cystic Fibrosis Foundation, endorsed by the Pediatric Endocrine 
Society. Diabetes Care. Dec 2010;33(12):2697-708. doi:10.2337/dc10-1768 
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active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. Research 
Support, Non-U.S. Gov't. J Cyst Fibros. Mar 2012;11(2):144-9. doi:10.1016/j.jcf.2011.11.001 
17. 
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in Diabetes-2022. Diabetes Care. Jan 01 2022;45(Supplement_1):S83-S96. doi:10.2337/dc22-
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21. 
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22. 
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cystic fibrosis community to optimize assessment of gastrointestinal symptoms. J Cyst Fibros. 
Jan 12 2021;doi:10.1016/j.jcf.2020.12.021 
23. 
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information.   https://www.ozempic.com/prescribing-information.html. Accessed August 9, 
2021,  
24. 
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lowering medications and the risk of acute pancreatitis and malignancies: a meta-analysis based 
on cardiovascular outcomes trials. Diabetes Obes Metab. 04 2020;22(4):699-704. 
doi:10.1111/dom.13924