Type 1 DiabetesDARENCT01272583
Dipeptidyl Peptidase-4 Inhibitors and Alpha-cell Recovery
A study testing Sitagliptin in people with Type 1 Diabetes and Hypoglycemia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
Trial summary
Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. Read more about this study
- Who is it for?
- Ages 18 to 55 years, men only
- Conditions the study is for
- Type 1 Diabetes, Hypoglycemia
- What is being tested?
- Sitagliptin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Mar 2011to Oct 2012
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- Men only
- No healthy volunteers
- Adult
Who may be able to join
- Type 1 Diabetes Mellitus 5-20 years duration
- C-peptide negative
- Willing and able to give written informed consent
Who cannot join
- Impaired awareness of hypoglycaemia
- BMI > 27 kg/m2
- Evidence of severe diabetes complications (autonomic neuropathy, macroalbuminuria, proliferative retinopathy)
- Acute illness within 3 months before the study
- Significant renal impairment (creatinine clearance < 50ml/min)
- Use of beta-adrenoreceptor blockers
- Cardiac history (previous arrhythmia)
- History of epilepsy
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Academic Medical Center
Amsterdam, North Holland, 1100DD
About this study
Official title: Effects of 6 Weeks Treatment With a Dipeptidyl Peptidase 4 Inhibitor on Counterregulatory and Incretin Hormones During Acute Hypoglycaemia in Patients With Type 1 Diabetes: a Randomized Double Blind Placebo-controlled Cross-over Study
Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. Dipeptidyl Peptidase (DPP)-4 inhibitors augment the glucagon response to insulin-induced hypoglycaemia in type 2 diabetes. The investigators hypothesize that treatment with a DPP-4 inhibitor in patients with type 1 diabetes will recover the alpha cell response to hypoglycaemia.
Read the detailed description
The 16 type 1 patients will be randomised to one of two treatment sequences: DPP-4 inhibitor followed by placebo or placebo followed by a DPP-4 inhibitor. Each treatment period lasts 6 weeks, so all patients will receive treatment for 12 weeks in total. Induction of hypoglycaemia will take place at 0 weeks, 6 weeks and 12 weeks to determine the glucagon response.
- Conditions
- Type 1 Diabetes, Hypoglycemia
- Being tested
- Sitagliptin, Placebo
- Keywords
- Type 1 diabetes, DPP-4 inhibitor, Glucagon
- 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.
SitagliptinDrug
Also called Januvia
100 mg once daily for six weeks
PlaceboDrug
placebo, once daily for six weeks
| Study group | Role | What they receive |
|---|---|---|
| Sequence A (sitagliptin→placebo) | Other | Cross-over, both arms reveived the same intervention in different order. Receives: Drug: Sitagliptin; Drug: Placebo |
| Sequence B (placebo→sitagliptin) | Other | Cross-over, both arms reveived the same intervention in different order. Receives: Drug: Sitagliptin; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glucagon Response to Acute Hypoglycaemia
Change in glucagon concentration from the initialisation phase to 40 minutes after occurrence of the autonomic reaction to hypoglycaemia
Measured: Change from initialisation phase to 40 minutes after onset of hypoglycaemia
Glucagon Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Measured: 0, 10, 20 and 40 minutes
Secondary outcomes (6)
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Measured: 0, 10, 20, 40 minutes
Epinephrine Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Measured: 0, 10, 20, 40 minutes
Norepinephrine Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Measured: 0, 10, 20, 40 minutes
Growth Hormone Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Measured: 0, 10, 20, 40 minutes
Cortisol Response to Acute Hypoglycaemia
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
Measured: 0, 10, 20, 40 minutes
Symptomatic Hormone Responses to Acute Hypoglycaemia.
The symptomatic responses to hypoglycaemia were assessed using a standard validated symptom questionnaire adapted for experimental hypoglycaemia (McCrimmon et al (2003) Diabet.Med. 20: 507-509). A 7-point Likert scale (1=symptom absent; 7=symptom experienced with great intensity) was used to score presence and intensity of autonomic and neuroglycopenic symptoms of hypoglycaemia. Symptom scores were obtained during the initialisation phase, at occurrence of autonomic reaction and again 30 minutes later. For analyses the scale was considered as a continuous variable.
Measured: Change from baseline symptomatic response at hypoglycaemia and 30 minutes after hypoglycaemia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2011 (estimated)
- Study startMar 2011
- Primary completionJun 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type 1 DiabetesStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The 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
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Principal investigator, F Holleman, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Frits Holleman, MD,PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01272583
- Sponsor's protocol ID
- DARE_2010
- Acronym
- DARE
- Status last verified
- Feb 2014
- First submitted
- 5 Jan 2011
- Last updated
- 14 Mar 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Mar 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of 6 Weeks Treatment With a Dipeptidyl Peptidase 4 Inhibitor on Counterregulatory and Incretin Hormones During Acute Hypoglycaemia in Patients With Type 1 Diabetes: a Randomized Double Blind Placebo-controlled Cross-over Study
- ClinicalTrials.gov ID
- NCT01272583
- Acronym / sponsor ID
- DARE / DARE_2010
- Conditions
- Type 1 Diabetes, Hypoglycemia
- Keywords
- Type 1 diabetes, DPP-4 inhibitor, Glucagon
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- Mar 2011
- Primary completion
- Jun 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 10 Jan 2011 (estimated)
- Results
- Posted 17 Feb 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Hypoglycaemia is a well-known complication of insulin treated diabetes. The counterregulatory response to hypoglycaemia, with glucagon as the most important mediator, is initially diminished within a few years of onset of Type 1 diabetes and subsequently lost and thus increasing the risk of hypoglycaemia. Dipeptidyl Peptidase (DPP)-4 inhibitors augment the glucagon response to insulin-induced hypoglycaemia in type 2 diabetes. The investigators hypothesize that treatment with a DPP-4 inhibitor in patients with type 1 diabetes will recover the alpha cell response to hypoglycaemia.
Detailed description
The 16 type 1 patients will be randomised to one of two treatment sequences: DPP-4 inhibitor followed by placebo or placebo followed by a DPP-4 inhibitor. Each treatment period lasts 6 weeks, so all patients will receive treatment for 12 weeks in total. Induction of hypoglycaemia will take place at 0 weeks, 6 weeks and 12 weeks to determine the glucagon response.
Study design
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sequence A (sitagliptin→placebo) | Other | Drug: Sitagliptin, Drug: PlaceboCross-over, both arms reveived the same intervention in different order. |
| Sequence B (placebo→sitagliptin) | Other | Drug: Sitagliptin, Drug: PlaceboCross-over, both arms reveived the same intervention in different order. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Type 1 Diabetes Mellitus 5-20 years duration
- C-peptide negative
- Willing and able to give written informed consent
Key exclusion criteria (8 listed)
- Impaired awareness of hypoglycaemia
- BMI > 27 kg/m2
- Evidence of severe diabetes complications (autonomic neuropathy, macroalbuminuria, proliferative retinopathy)
- Acute illness within 3 months before the study
- Significant renal impairment (creatinine clearance < 50ml/min)
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 |
|---|---|---|
| SitagliptinAlso: Januvia100 mg once daily for six weeks | Drug | Sequence A (sitagliptin→placebo), Sequence B (placebo→sitagliptin) |
| Placeboplacebo, once daily for six weeks | Drug | Sequence A (sitagliptin→placebo), Sequence B (placebo→sitagliptin) |
Primary outcome
Glucagon Response to Acute Hypoglycaemia
Time frame: Change from initialisation phase to 40 minutes after onset of hypoglycaemia
Change in glucagon concentration from the initialisation phase to 40 minutes after occurrence of the autonomic reaction to hypoglycaemia
Glucagon Response to Acute Hypoglycaemia
Time frame: 0, 10, 20 and 40 minutes
Area under the curve (AUC) from onset of the autonomic response to hypoglycaemia to 40 minutes after onset of the autonomic response. AUC values were calculated by the trapezoid method.
6 secondary outcomes
Intact and Total Glucagon Like Peptide-1 (GLP-1), Intact and Total Gastric Inhibitory Peptide (GIP) Response to Acute Hypoglycaemia
Time frame: 0, 10, 20, 40 minutes
Epinephrine Response to Acute Hypoglycaemia
Time frame: 0, 10, 20, 40 minutes
Norepinephrine Response to Acute Hypoglycaemia
Time frame: 0, 10, 20, 40 minutes
Growth Hormone Response to Acute Hypoglycaemia
Time frame: 0, 10, 20, 40 minutes
Cortisol Response to Acute Hypoglycaemia
Time frame: 0, 10, 20, 40 minutes
Symptomatic Hormone Responses to Acute Hypoglycaemia.
Time frame: Change from baseline symptomatic response at hypoglycaemia and 30 minutes after hypoglycaemia
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Mar 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Frits Holleman, MD,PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sitagliptin in people with Type 1 Diabetes and Hypoglycemia, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 1 site in Netherlands.
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 3 inclusion and 8 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 14 Mar 2014. 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 Netherlands. 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?
Yes. Results are posted in the registry (first posted 17 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Glucagon Response to Acute Hypoglycaemia (time frame: Change from initialisation phase to 40 minutes after onset of hypoglycaemia). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Mar 2014.