Type 1 DiabetesPhase 3NCT01922817
DPP4inhibitors in Type 1 Diabetes
A Phase 3 study testing Saxagliptin in people with Type 1 Diabetes and Hypoglycaemia, run by University of Dundee at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Type 1 Diabetes, Hypoglycaemia
- What is being tested?
- Saxagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 28 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Sep 2012to Apr 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical research centre, Ninewells Hospital and Medical School
Dundee, DD1 9SY
About this study
Official title: A Dipeptidyl Peptidase 4 (DPP-4) Inhibitor in Type 1 Diabetes
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.
Read the 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.
- Conditions
- Type 1 Diabetes, Hypoglycaemia
- Being tested
- Saxagliptin
- Medical subject headings
- Diabetes Mellitus, Type 1, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SaxagliptinDrug
5mg saxagliptin
| Study group | Role | What they receive |
|---|---|---|
| Saxagliptin | Active comparator | 5mg once daily in addition to insulin therapy Receives: Drug: Saxagliptin |
| Placebo | Placebo comparator | Crossover Placebo once daily Receives: Drug: Saxagliptin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Magnitude of epinephrine release at 2.5mmol/L
Measured: During hyperinsulinaemic hypoglycaemia clamp
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2013 (estimated)
- Study startSep 2012
- Primary completionApr 2014
- Study completionApr 2014
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 Type 1 DiabetesStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- crossover trial between Saxaglipin and Placebo with 2 week washout in between
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Dundee
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01922817
- Sponsor's protocol ID
- 2012DM07
- Status last verified
- Oct 2019
- First submitted
- 6 Aug 2013
- Last updated
- 15 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
George PS, McCrimmon RJ. Saxagliptin co-therapy in C-peptide negative Type 1 diabetes does not improve counter-regulatory responses to hypoglycaemia. Diabet Med. 2016 Sep;33(9):1283-90. doi: 10.1111/dme.13046. Epub 2015 Dec 28.
PubMed 26642301
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dipeptidyl Peptidase 4 (DPP-4) Inhibitor in Type 1 Diabetes
- ClinicalTrials.gov ID
- NCT01922817
- Acronym / sponsor ID
- 2012DM07
- Conditions
- Type 1 Diabetes, Hypoglycaemia
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- University of DundeeUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 14 Aug 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.
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.
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
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- crossover trial between Saxaglipin and Placebo with 2 week washout in between
| Arm | Type | Receives |
|---|---|---|
| Saxagliptin | Active comparator | Drug: Saxagliptin5mg once daily in addition to insulin therapy |
| Placebo | Placebo comparator | Drug: SaxagliptinCrossover Placebo once daily |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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
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 |
|---|---|---|
| Saxagliptin5mg saxagliptin | Drug | Placebo, Saxagliptin |
Primary outcome
Magnitude of epinephrine release at 2.5mmol/L
Time frame: During hyperinsulinaemic hypoglycaemia clamp
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2019.
- Background: PubMed 26642301George PS, McCrimmon RJ. Saxagliptin co-therapy in C-peptide negative Type 1 diabetes does not improve counter-regulatory responses to hypoglycaemia. Diabet Med. 2016 Sep;33(9):1283-90. doi: 10.1111/dme.13046. Epub 2015 Dec 28.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Saxagliptin in people with Type 1 Diabetes and Hypoglycaemia, run by University of Dundee at 1 site in United Kingdom.
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 6 inclusion and 12 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: finished, as of the sponsor's last update on 15 Oct 2019. 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 Kingdom. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Magnitude of epinephrine release at 2.5mmol/L (time frame: During hyperinsulinaemic hypoglycaemia clamp). 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 NCT01922817, 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 15 Oct 2019.