DPP-IV Inhibition Prior to Development of Diabetes in Patients With Cystic Fibrosis

NCT02239458 | Unknown

• 1 other identifier: 0388-14-HMO
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Cystic fibrosis related diabetes (CFRD) is a common co-morbidity in patients with CF. The underlying pathophysiology of cystic fibrosis related diabetes (CFRD) is still a matter of investigation. In addition to localized tissue damage developing similar to that of the exocrine pancreas, other mechanisms may be involved. We have shown that a potential contributing factor to the patho-physiology of CFRD may be an abnormal gut derived hormonal profile, specifically of lower incretin hormone responses, prior to development of CFRD. We propose that an altered incretin response, probably due to impaired interaction of nutrients with the gut mucosa due to thickened secretions, may play a role in the development of the disease. Specifically, low GIP and GLP-1, may explain the poor β-cell function observed in these patients prior to CFRD appearance. These incretins have known trophic effects on β-cells, and thus their lower levels may contribute to the development of quantitative as well as qualitative defects in β-cell function and thus may lead to the development of CFRD. Thus, increasing levels of these incretins using a DPP-IV inhibitor may improve glucose metabolism and delay/prevent the development of CFRD. We hypothesize that Saxagliptin will increase the oDI compared to placebo and will thus provide relative protection from diabetes development and in addition we expect that Saxagliptin will lead to overall increased insulin concentrations and thus shift the metabolic milieu to a more anabolic state. This will manifest as weight gain and reduction in inflammation.

Conditions

Cystic Fibrosis

Outcome Measures

Primary Outcomes (1)

• Oral Disposition Index

  The oDI is a useful predictor of diabetes development over time and its increase will provide evidence for protection from diabetes in this special study population

  The ODI will be calculated at baseline (Day 1) and at End point (day 90- 3 months)

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo intake during 3 months

Saxagliptin 5mg

ACTIVE COMPARATOR

Saxagliptin dose of 5mg for 3 months

Drug: Saxagliptin

Interventions

Saxagliptin DRUG

Also known as: Onglyza

Saxagliptin 5mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than 18 years
• Diagnosis of CF
• No CFRD on baseline OGTT
• Normal kidney function
• No history of pancreatitis
• Able and willing to consent and participate

You may not qualify if:

• Acute illness/exacerbation of CF associated lung disease
• Receiving immune-modulators following lung/pancreas transplant

Sponsors & Collaborators

• Ram Weiss: lead

Study Sites (1)

Hadassah Ein Kerem/Har Hazofim

Jerusalem, 91120, Israel

Location

MeSH Terms

Conditions

Cystic Fibrosis

Interventions

saxagliptin

Condition Hierarchy (Ancestors)

Pancreatic Diseases; Digestive System Diseases; Lung Diseases; Respiratory Tract Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases

Study Officials

• Eitan Kerem, MD

  Hadassah Ein Kerem

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ram Weiss, MD PhD

CONTACT

+972-50-894-6469; ramw@ekmd.huji.ac.il

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of the Department of Human Metabolism and Nutrition

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 12, 2014
• Study Start: June 1, 2015
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: April 16, 2015

Record last verified: 2014-09

Locations

IL (1)