Cystic FibrosisNCT01851694
Beta-cell Response to Incretin Hormones in Cystic Fibrosis
A study testing GLP-1 and GIP in people with Cystic Fibrosis and Pancreatic Insufficiency, run by University of Pennsylvania at 1 site in United States.
Trial summary
In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 (T1D) and Type 2 (T2D) diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin, respectively. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Cystic Fibrosis, Pancreatic Insufficiency
- What is being tested?
- GLP-1 and GIP
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- May 2013to Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
- Age greater than or equal to 18y on date of consent
- Pancreatic insufficiency
- Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
- For female subjects, negative urine pregnancy test at enrollment.
- Control Subjects:
Show all 10Show fewer
- No history of cystic fibrosis.
- Age ≥ 18y on date of consent.
- Recent OGTT consistent with NGT.
- For female subjects, negative urine pregnancy test at enrollment.
Who cannot join
- Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
- History of clinically symptomatic pancreatitis within last year
- Prior lung or liver transplant
- Severe CF liver disease, as defined by portal hypertension
- Fundoplication-related dumping syndrome
- Medical co-morbidities that are not CF-related or are unstable per investigator opinion (i.e. history of bleeding disorders, immunodeficiency)
Show all 21Show fewer
- Acute illness or changes in therapy (including antibiotics) within 6 weeks prior to study procedures
- Treatment with oral or intravenous corticosteroids within 6 weeks of study
- Hemoglobin less than10g/dL, within 90 days of Visit 1 or at Screening
- Abnormal renal function, within 90 days of Visit 1 or at Screening; defined as Creatinine greater than 2x upper limit of normal (ULN) or potassium greater than 5.5mEq/L on non-hemolyzed specimen
- Inability to perform study specific procedures (MMTT, GPA)
- Subjects, who in study team opinion, may be non-compliant with study procedures.
- Control Subjects who will be exposed to GIP only:
- History of clinically symptomatic pancreatitis.
- History of liver disease.
- History of any illness or condition that, in the opinion of the investigator might confound the results of the study or pose an additional risk to the subject.
- Hemoglobin <10g/dL, within 90 days of GPA test or at Screening.
- Abnormal renal function, within 90 days of GPA test or at Screening; defined as creatinine > 2x upper limit of normal (ULN) or potassium > 5.5mEq/L on non-hemolyzed specimen.
- Inability to perform study specific procedures (MMTT, GPA).
- subjects, who in study team opinion, may be non-compliant with study procedures.
- elevation of serum amylase or lipase > 1.5x ULN within 90 days of GPA test.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Philadelphia and University of Pennsylvania
Philadelphia, Pennsylvania, 19060
Paola Alvarado, 215-746-2081, paola.alvarado@pennmedicine.upenn.edu
Michael Rickels, M.D., M.S
About this study
Official title: Determination of Beta-cell Responsiveness to the Incretin Hormones GLP-1 and GIP in Cystic Fibrosis
In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 (T1D) and Type 2 (T2D) diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin, respectively. Insulin is a hormone which is made by cells in the pancreas and helps carry glucose (sugar) from the food we eat to the cells of the body for energy. While cystic fibrosis related diabetes (CFRD) has many features similar to both T1D and T2D, patients with CF may not have the same symptoms as either T1D or T2D patients. Currently, there is little understanding of CFRD and the best options for treatment remain unclear.
The purpose of this research study is to examine and understand the various mechanisms that contribute to CFRD and gain a better understanding of potential means to treat CFRD. In particular, we plan to study the effects of incretin hormones that can enhance insulin production in CF patients.
Read more
Enrollment is complete for the protocol as initially written. In order to further study the role of the incretin hormone on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function , we have received approval to extend our investigation to include the following study groups:
- Cystic Fibrosis participants with normal glucose tolerance
- Non-Cystic Fibrosis controls
Read the detailed description
Previously, cystic fibrosis related diabetes (CFRD) was considered to be a consequence of damage to the pancreas therefore the cells contained in the pancreas--i.e.--islets that house beta cells, which make and release insulin (similar to T1D). Recent evidence suggests that other factors may also be associated that are similar to those with T2D. For example, patients with T2D, have decreased secretion of incretins, hormones released by the small intestine in response to nutrients from food which act, among other things, to increase insulin secretion from Beta cells of the pancreas. When patients with T2D are treated with incretin hormones, their pancreatic Beta cells release more insulin (measured as 'second phase insulin secretion'). Currently, we do not know if patients with CFRD have decreased incretin secretion like T2D or if treating CFRD patients with incretin hormones will improve their insulin levels. This study will measure insulin release from the Beta cells from CFRD patients (second phase insulin secretion) that are being given incretin hormones in the veins. This will be compared with insulin release when the same patients are given a placebo (salt containing solution). The patients and the research team will not know what is being given until all the results are collected. The results will provide unbiased evidence if incretins will help improve insulin release in CFRD patients.
- Conditions
- Cystic Fibrosis, Pancreatic Insufficiency
- Being tested
- GLP-1, GIP
- Keywords
- Cystic Fibrosis, Diabetes, Pancreatic insufficiency, Cystic Fibrosis with Normal Glucose Tolerance, Non-Cystic Fibrosis control group
- Medical subject headings
- Cystic Fibrosis, Exocrine Pancreatic Insufficiency, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP-1Drug
Each subject in this arm will receive GLP-1 infusion and a placebo infusion during a GPA test.
GIPDrug
Also called Glucose-dependent insulinotrophic polypeptide
Each subject in this arm will receive GIP infusion and placebo during a GPA test.
| Study group | Role | What they receive |
|---|---|---|
| GLP-1 Incretin Hormone | Experimental | The incretin, Glucagon-Like-peptide-1 (GLP-1) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins. (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion. Receives: Drug: GLP-1 |
| GIP Incretin Hormone | Experimental | The incretin, Glucose-dependent Insulinotropic Polypeptide (GIP) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion. Receives: Drug: GIP |
What is being measured
The primary outcome is the main question the study is designed to answer.
Second-phase insulin response during GPA test
The key endpoint of interest will be the change in second phase insulin response derived from the Glucose-Potentiated Arginine (GPA) test. The GPA test will measure insulin (and other glucose controlling hormones) which will be a measure of pancreatic endocrine function in response to injection of arginine. Arginine is a naturally occurring amino acid (substance) in the body. It will be given in the veins to make the pancreas secrete insulin. After the first injection of arginine, a glucose infusion will be started in order to raise the level of sugar in the blood to 230 mg/dl. Once the level is achieved, arginine will be injected again and blood samples are measured. After a 2 hour break, the glucose infusion will be started to achieve a blood sugar of 340mg/dl and arginine injection will be repeated. Comparison of responses with incretin vs. placebo will be performed using statistical methods, specifically, paired t-test or Wilcoxon matched pair test.
Measured: 5 hours
Secondary outcomes (1)
Change in insulin secretion among CF groups
The change in second phase insulin secretion induced by incretins will be compared among the different subgroups of patients with CF (Ind-GT, IGT, and early CFRD) groups using nonparametric comparison of changes in slope, estimated using Mann-Whitney methods.
Measured: 5 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2013 (estimated)
- Study startMay 2013
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Responsible party
- Principal investigator, Michael R. Rickels, MD, MS, University of Pennsylvania
- Investigators
- Michael R. Rickels, MD, MS, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01851694
- Sponsor's protocol ID
- 817585
- Status last verified
- Jan 2026
- First submitted
- 8 May 2013
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Upon completion of enrollment, once our data has been analyzed.
Publications
Nyirjesy SC, Peleckis AJ, Eiel JN, Gallagher K, Doliba A, Tami A, Flatt AJ, De Leon DD, Hadjiliadis D, Sheikh S, Stefanovski D, Gallop R, D'Alessio DA, Rubenstein RC, Kelly A, Rickels MR. Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis. Diabetes. 2022 Oct 1;71(10):2153-2165. doi: 10.2337/db22-0399.
PubMed 35796669
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Determination of Beta-cell Responsiveness to the Incretin Hormones GLP-1 and GIP in Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT01851694
- Acronym / sponsor ID
- 817585
- Conditions
- Cystic Fibrosis, Pancreatic Insufficiency
- Keywords
- Cystic Fibrosis, Diabetes, Pancreatic insufficiency, Cystic Fibrosis with Normal Glucose Tolerance, Non-Cystic Fibrosis control group
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Collaborators
- Children's Hospital of Philadelphia
- Study start
- May 2013
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 10 May 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In recent years, diabetes has emerged as one of the most significant co-diseases that many Cystic Fibrosis (CF) patients develop. Type 1 (T1D) and Type 2 (T2D) diabetes results when either the body does not make enough insulin or the body does not respond correctly to this insulin, respectively. Insulin is a hormone which is made by cells in the pancreas and helps carry glucose (sugar) from the food we eat to the cells of the body for energy. While cystic fibrosis related diabetes (CFRD) has many features similar to both T1D and T2D, patients with CF may not have the same symptoms as either T1D or T2D patients. Currently, there is little understanding of CFRD and the best options for treatment remain unclear.
The purpose of this research study is to examine and understand the various mechanisms that contribute to CFRD and gain a better understanding of potential means to treat CFRD. In particular, we plan to study the effects of incretin hormones that can enhance insulin production in CF patients.
Enrollment is complete for the protocol as initially written. In order to further study the role of the incretin hormone on Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function , we have received approval to extend our investigation to include the following study groups:
- Cystic Fibrosis participants with normal glucose tolerance
- Non-Cystic Fibrosis controls
Detailed description
Previously, cystic fibrosis related diabetes (CFRD) was considered to be a consequence of damage to the pancreas therefore the cells contained in the pancreas--i.e.--islets that house beta cells, which make and release insulin (similar to T1D). Recent evidence suggests that other factors may also be associated that are similar to those with T2D. For example, patients with T2D, have decreased secretion of incretins, hormones released by the small intestine in response to nutrients from food which act, among other things, to increase insulin secretion from Beta cells of the pancreas. When patients with T2D are treated with incretin hormones, their pancreatic Beta cells release more insulin (measured as 'second phase insulin secretion'). Currently, we do not know if patients with CFRD have decreased incretin secretion like T2D or if treating CFRD patients with incretin hormones will improve their insulin levels. This study will measure insulin release from the Beta cells from CFRD patients (second phase insulin secretion) that are being given incretin hormones in the veins. This will be compared with insulin release when the same patients are given a placebo (salt containing solution). The patients and the research team will not know what is being given until all the results are collected. The results will provide unbiased evidence if incretins will help improve insulin release in CFRD patients.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GLP-1 Incretin Hormone | Experimental | Drug: GLP-1The incretin, Glucagon-Like-peptide-1 (GLP-1) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins. (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion. |
| GIP Incretin Hormone | Experimental | Drug: GIPThe incretin, Glucose-dependent Insulinotropic Polypeptide (GIP) will be infused into the veins starting 30 minutes prior to initiating the GPA test. This infusion will continue for a total of 90 mins (during the GPA for 230 mg/dL glucose levels) and then this will be stopped. The GPA test will be performed for the 340 mg/dL glucose levels but no incretin will be infused during this part of the test. These data will be compared when the subject repeats the GPA test with a placebo (saline or salt containing solution) infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Confirmed diagnosis of cystic fibrosis, defined by positive sweat test or CFTR mutation analysis according to CFF diagnostic criteria,
- Age greater than or equal to 18y on date of consent
- Pancreatic insufficiency
- Recent OGTT consistent with Indeterminate-GT, IGT, CFRD w/o fasting hyperglycemia, or an established diagnosis of CFRD without fasting hyperglycemia
- For female subjects, negative urine pregnancy test at enrollment.
Key exclusion criteria (21 listed)
- Established diagnosis of non-CF diabetes (i.e. T1D) or CFRD with fasting hyperglycemia (fasting glucose greater than126 mg/dL)
- History of clinically symptomatic pancreatitis within last year
- Prior lung or liver transplant
- Severe CF liver disease, as defined by portal hypertension
- Fundoplication-related dumping syndrome
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GLP-1Each subject in this arm will receive GLP-1 infusion and a placebo infusion during a GPA test. | Drug | GLP-1 Incretin Hormone |
| GIPAlso: Glucose-dependent insulinotrophic polypeptideEach subject in this arm will receive GIP infusion and placebo during a GPA test. | Drug | GIP Incretin Hormone |
Primary outcome
Second-phase insulin response during GPA test
Time frame: 5 hours
The key endpoint of interest will be the change in second phase insulin response derived from the Glucose-Potentiated Arginine (GPA) test. The GPA test will measure insulin (and other glucose controlling hormones) which will be a measure of pancreatic endocrine function in response to injection of arginine. Arginine is a naturally occurring amino acid (substance) in the body. It will be given in the veins to make the pancreas secrete insulin. After the first injection of arginine, a glucose infusion will be started in order to raise the level of sugar in the blood to 230 mg/dl. Once the level is achieved, arginine will be injected again and blood samples are measured. After a 2 hour break, the glucose infusion will be started to achieve a blood sugar of 340mg/dl and arginine injection will be repeated. Comparison of responses with incretin vs. placebo will be performed using statistical methods, specifically, paired t-test or Wilcoxon matched pair test.
1 secondary outcome
Change in insulin secretion among CF groups
Time frame: 5 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Derived from this study: PubMed 35796669Nyirjesy SC, Peleckis AJ, Eiel JN, Gallagher K, Doliba A, Tami A, Flatt AJ, De Leon DD, Hadjiliadis D, Sheikh S, Stefanovski D, Gallop R, D'Alessio DA, Rubenstein RC, Kelly A, Rickels MR. Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis. Diabetes. 2022 Oct 1;71(10):2153-2165. doi: 10.2337/db22-0399.
- Individual participant dataSharing planned: Yes. Upon completion of enrollment, once our data has been analyzed.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael R. Rickels, MD, MS principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GLP-1 and GIP in people with Cystic Fibrosis and Pancreatic Insufficiency, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Paola Alvarado (215-746-2081, paola.alvarado@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Second-phase insulin response during GPA test (time frame: 5 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01851694, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.