DPP4inhibitors in Type 1 Diabetes

Sponsor

University of Dundee (Other)

Overall Status

Completed

CT.gov ID

NCT01922817

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A small, pilot, randomised, cross over trial that investigates the potential for DPPIVi therapy to reduce insulin requirements in type 1 diabetes was studied. We investigated whether this drug reduces daily insulin doses, leads to weight reduction, reduces blood glucose fluctuation and improves glucose control. Through reduction of blood glucose variability, we want investigated, whether it has the capability of improving the magnitude of epinephrine responses at 2.5mmol/L by performing a hyperinsulinaemic, hypoglycaemia clamp study after each arm. A successful outcome would then lead to an application for funds for a larger, multicentre intervention study. The benefits of this therapeutic advance are clear and this has the potential to make a dramatic improvement to the lives of people with type 1 diabetes in our community.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Hypoglycaemia	Drug: Saxagliptin	Phase 3

Detailed Description

Ninety years ago the discovery of insulin and its development as a drug revolutionized the management of type 1 diabetes, which until that point had almost inevitably proven fatal. However, very rapidly it was recognized that like all "wonder" drugs there were problems with insulin. Elliot Joslin, one of the pioneers of diabetes therapy described insulin as "…a potent preparation alike for evil and for good"(1922). There are two major reasons for this. Firstly, in non-diabetic individuals insulin produced by the pancreas acts directly on the liver, the major organ for regulating blood glucose levels. In contrast, people with type 1 diabetes inject insulin under the skin, and this is then absorbed into the circulation and much of it is degraded (~50%) before it gets to the liver. This means that in order to act effectively in the liver a type 1 diabetic needs to inject at least double the amount of insulin. Many studies have now shown that high insulin levels lead to weight gain, accelerated blood vessel disease (atherosclerosis) and a higher risk of suffering low blood glucose (hypoglycaemia). A second major problem is that individuals with type 1 show high levels of the hormone, glucagon. Glucagon is also produced in the pancreas and is normally regulated by pancreatic insulin, so the loss of this effect in people with type 1 diabetes means they run high glucagon levels. This has been shown to increase blood glucose, particularly after a meal. It is because of this that the diabetes community has called for novel therapies that can reduce high insulin levels and high glucagon levels. A new class of drugs called dipeptidylpeptidase IV inhibitors (DPPIVi) are currently used to treat people with type 2 diabetes. DPPIV inhibition increases endogenous levels of glucagon like peptide-1 (GLP-1). These drugs have a number of actions but the most relevant to this application is that they directly suppress glucagon, induce satiety (i.e. reduce hunger and leads to a reduction in body weight) and indirectly reduce the need for high dose insulin injections. This makes them an ideal candidate drug as an insulin sparing or adjunct therapy in type 1 diabetes, but there is very limited data to date for this use.

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

crossover trial between Saxaglipin and Placebo with 2 week washout in betweencrossover trial between Saxaglipin and Placebo with 2 week washout in between

Masking:

Double (Participant, Investigator)

Masking Description:

double blind

Primary Purpose:

Prevention

Official Title:

A Dipeptidyl Peptidase 4 (DPP-4) Inhibitor in Type 1 Diabetes

Study Start Date :

Sep 1, 2012

Actual Primary Completion Date :

Apr 1, 2014

Actual Study Completion Date :

Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Saxagliptin 5mg once daily in addition to insulin therapy	Drug: Saxagliptin 5mg saxagliptin
Placebo Comparator: Placebo Crossover Placebo once daily	Drug: Saxagliptin 5mg saxagliptin

Arm

Intervention/Treatment

Active Comparator: Saxagliptin

5mg once daily in addition to insulin therapy

Drug: Saxagliptin

5mg saxagliptin

Placebo Comparator: Placebo

Crossover Placebo once daily

Drug: Saxagliptin

5mg saxagliptin

Outcome Measures

Primary Outcome Measures

Magnitude of epinephrine release at 2.5mmol/L [During hyperinsulinaemic hypoglycaemia clamp]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria;

Type 1 diabetes over 5 years duration
HbA1c less than 10%
Age 18 and over
Current use of intensive insulin therapy (injections or pump)
BMI 19-35
Ability to give written informed consent to participate in the study

Exclusion criteria;

Previous history of pancreatic disease/cancer
Significant renal disease estimated glomerular filtration rate (eGFR) less than 50
Significant microvascular disease
Personal/family history of Medullary thyroid cancer
Personal/family history of multiple endocrine neoplasia (MEN) Type 2
Moderate/Severe hepatic impairment
Pregnancy or breast feeding
History of epilepsy/hypoglycaemia induced seizure
Those on any other hypoglycaemia drug apart from insulin for their diabetes.
Currently on CYP3A4 inducers like carbamazepine, dexamethasone, phenobarbital, phenytoin, rifampicin
Currently on CYP3A4 inhibitors like ketoconazole, diltiazem
Less than 30 days since participation in another drug trial or longer depending on the drug half life.