DiabetesPhase 4NCT00509925

Effect of Insulin Detemir on Use of Energy in Type 1 Diabetes

A Phase 4 study testing insulin detemir, insulin NPH and insulin aspart in people with Diabetes and Diabetes Mellitus, Type 1, run by Novo Nordisk A/S at 1 site in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This trial is conducted in Europe. The purpose of this trial is to investigate if there is any change in the mechanism of energy expenditure (i.e. the way in which energy is used) in patients with type 1 diabetes, whilst taking two different, commercially available insulins for the treatment of their diabetes. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Diabetes, Diabetes Mellitus, Type 1
What is being tested?: insulin detemir, insulin NPH and insulin aspart
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 23 participants
Where: 1 siteUnited Kingdom
Study dates: Jul 2007to Jul 2008
Phase: Phase 4
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 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Type 1 diabetes for more than 12 months
Current treatment: Basal-bolus insulin regimen for more than three months (i.e. at least one daily injection of long-acting insulin (including insulin glargine) and fast-acting insulin with each main meal)
HbA1c (glycosylated haemoglobin A1c) between 7.0 and 11.0%
Able and willing to maintain consistent physical activity level throughout the entire study period
Able and willing to maintain consistent eating habits throughout the entire study period

Who cannot join

Proliferative retinopathy that has required acute treatment within the last six months
Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator
Liver, kidney or heart problems as judged by the Investigator
Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures
Known or suspected allergy to trial products or related products
Receipt of any investigational drug within one month prior to this trial

Trial locations and contacts

1 site in 1 country.

United Kingdom1 site

Novo Nordisk Investigational Site
Guildford, GU2 7XX

Other trials in United Kingdom

About this study

Official title: A 32-week National, Single-centre, Open-labelled, Randomised, Crossover Trial Comparing Energy Expenditure With Insulin Detemir Versus NPH Insulin Using a Basal-Bolus Regimen With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes

Read the detailed description

The study had been temporarily halted due to an unplanned interim analysis. The Sponsor is now aware that a further interim analysis has been performed by the site and therefore a decision has been made not to recommence the study

Conditions: Diabetes, Diabetes Mellitus, Type 1
Being tested: insulin detemir, insulin NPH, insulin aspart
Medical subject headings: Diabetes Mellitus, Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

insulin detemirDrug
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
insulin NPHDrug
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection
insulin aspartDrug
Treat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection

Study groups in NCT00509925
Study group	Role	What they receive
Treatment period 1	Experimental	Insulin detemir for 16 weeks (treatment period 1) followed by insulin NPH treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart Receives: Drug: insulin detemir; Drug: insulin NPH; Drug: insulin aspart
Treatment period 2	Experimental	Insulin NPH for 16 weeks (treatment period 1) followed by insulin detemir treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart Receives: Drug: insulin detemir; Drug: insulin NPH; Drug: insulin aspart

What is being measured

The primary outcome is the main question the study is designed to answer.

Total Energy Expenditure, Double-labelled Water Method
Total energy expenditure (TEE) measured after each treatment period by the double-labelled water (DLW) method. This technique required subjects to label their body water using oral administration of water labelled with 2 stable isotopes (2H218O). The clearance of 2H and 18O was measured over a two week period with daily collections of urine. The difference between the clearance of 2H and 18O is a measure of CO2 production rate. This can be converted to provide a measure of energy expenditure.
Measured: Weeks 14-16, weeks 30-32
Total Energy Expenditure, Dietary Record Method
The total energy expenditure (TEE) measured after each treatment period by the dietary record method. The calculation of energy balance is accomplished by compiling an accurate record of food intake over a period of time and measuring any changes in body weight that occur during that time. Data from the 7-day food diary was used to calculate TEE.
Measured: Weeks 14-16, weeks 30-32

Secondary outcomes (16)

Component of Total Energy Expenditure: Resting Energy Expenditure (REE)
Resting energy expenditure (REE) is a component of TEE (total energy expenditure). It was measured at 2 different timepoints during the trial using indirect calorimetry (measurement of O2 consumption/CO2 production) after an overnight fast when subjects would be metabolising a mixture of carbohydrate and free fatty acid. This technique allowed the calculation of the rate of carbohydrate and lipid oxidation.
Measured: Week 14, week 30
Component of Total Energy Expenditure: Diet Induced Thermogenesis (DIT)
Diet induced thermogenesis (DIT) is a component of TEE (total energy expenditure) and is the energy expenditure following feeding for anabolic processes. Subjects fasted overnight and rested for 1 hour. Multiple measurements of REE (resting energy expenditure) were taken. A fixed 600 kcal liquid meal was given and REE was measured over the next 3 hours. DIT was calculated as area under the curve of total REE-resting REE for the 3-hour period and was then converted to a per day measurement by taking into account each individual's average daily food intake.
Measured: Week 14, week 30
Component of Total Energy Expenditure: Physical Activity Thermogenesis
Physical activity thermogenesis is a component of TEE (total energy expenditure). Subjects were asked not to change their physical activity levels. Physical activity thermogenesis can be calculated as the difference between TEE minus (REE + DIT), as long as volitional exercise is unchanged. Volitional exercise was assessed using Actiheart 3-D monitor readings. Subjects were asked to measure their normal activity for between 1 and 5 days prior to their visits at week 16 and week 32).
Measured: Week 16, week 32
Component of Total Energy Expenditure: Non-exercise Activity Thermogenesis (NEAT)
Non-exercise activity thermogenesis is a component of TEE (total energy expenditure). Thermic efficiency was assessed by measuring O2 consumption/CO2 production while the subject exercised on a bike for 20 minutes while hooked up to a device that recorded their respiration (visit in week 14 and week 30). If thermic efficiency was unchanged and volitional exercise was unchanged, then any change in physical activity thermogenesis was due to changes in NEAT.
Measured: Week 16, week 32
Body Weight
Body weight after each treatment period.
Measured: Week 16, week 32
Lean Body Mass
Lean body mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Measured: Week 16, week 32
Fat Mass
Fat mass was measured using Bioelectrical Impedance Analysis (BIA), a method used for estimating body composition.
Measured: Week 16, week 32
Waist:Hip Ratio
At each time-point, 3 measurements each of waist and hip circumference were taken, then an average across the three measurements was calculated for both and the ratio was calculated as the waist average in cm divided by hip average in cm, and multiplied by 100.
Measured: Week 16, week 32
Hormonal Assessment: Adiponectin
Adiponectin levels after each treatment period.
Measured: Week 14, week 30
Hormonal Assessment: Insulin-like Growth Factor-1
Insulin-like growth factor-1 (IGF-1) levels after each treatment period.
Measured: Week 14, week 30
Hormonal Assessment: Resistin
Resistin levels after each treatment period.
Measured: Week 14, week 30
Hormonal Assessment: Leptin
Leptin levels after each treatment period.
Measured: Week 14, week 30
Glycosylated Haemoglobin A1c (HbA1c)
Glycosylated haemoglobin A1c (HbA1c) after each treatment period.
Measured: Week 16, week 32
Fasting Plasma Glucose
Fasting plasma glucose (FPG) after each treatment period.
Measured: Week 16, week 32
Hypoglycaemic Episodes
Total number of hypoglycaemic episodes experienced in the study.
Measured: Weeks 0-32
Hypoglycaemic Episodes, Diurnal/Nocturnal
Total number of hypoglycaemic episodes during the day (diurnal) and the night (nocturnal) experienced in the study.
Measured: Weeks 0-32

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2007Jul 2008

First posted1 Aug 2007 (estimated)
Study startJul 2007
Primary completionJul 2008
Study completionJul 2008

Why it stopped: See detailed description

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.
Publications (1)Papers the sponsor has linked to this study.
Other trials for DiabetesStudies of the same condition, open and under way.
More trials run by Novo Nordisk A/SThe 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 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 23 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00509925
Sponsor's protocol ID: NN304-1761
Other IDs: 2006-003060-59
Status last verified: Jan 2017
First submitted: 31 Jul 2007
Last updated: 10 Mar 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Zachariah S, Sheldon B, Shojaee-Moradie F, Jackson NC, Backhouse K, Johnsen S, Jones RH, Umpleby AM, Russell-Jones DL. Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes. Diabetes Care. 2011 Jul;34(7):1487-91. doi: 10.2337/dc11-0098. Epub 2011 May 18.
PubMed 21593292

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 10 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A 32-week National, Single-centre, Open-labelled, Randomised, Crossover Trial Comparing Energy Expenditure With Insulin Detemir Versus NPH Insulin Using a Basal-Bolus Regimen With Insulin Aspart as Mealtime Insulin in Subjects With Type 1 Diabetes
ClinicalTrials.gov ID: NCT00509925
Acronym / sponsor ID: NN304-1761
Conditions: Diabetes, Diabetes Mellitus, Type 1
Phase: Phase 4
Study type: Interventional
Recruitment status: TerminatedReason stopped: See detailed description
Enrolment: 23 participants (actual)
Lead sponsor: Novo Nordisk A/SIndustry (pharma, biotech, devices)
Study start: Jul 2007
Primary completion: Jul 2008 (actual)
Study completion: Jul 2008 (actual)
First posted: 1 Aug 2007 (estimated)
Results: Posted 4 Aug 2010

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Treatment period 1	Experimental	Drug: insulin detemir, Drug: insulin NPH, Drug: insulin aspartInsulin detemir for 16 weeks (treatment period 1) followed by insulin NPH treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart
Treatment period 2	Experimental	Drug: insulin detemir, Drug: insulin NPH, Drug: insulin aspartInsulin NPH for 16 weeks (treatment period 1) followed by insulin detemir treatment for 16 weeks (treatment period 2) in addition to meal-time insulin aspart

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Type 1 diabetes for more than 12 months
Current treatment: Basal-bolus insulin regimen for more than three months (i.e. at least one daily injection of long-acting insulin (including insulin glargine) and fast-acting insulin with each main meal)
HbA1c (glycosylated haemoglobin A1c) between 7.0 and 11.0%
Able and willing to maintain consistent physical activity level throughout the entire study period
Able and willing to maintain consistent eating habits throughout the entire study period

Key exclusion criteria (6 listed)

Proliferative retinopathy that has required acute treatment within the last six months
Recurrent major hypoglycaemia or hypoglycaemic unawareness as judged by the Investigator
Liver, kidney or heart problems as judged by the Investigator
Pregnancy, breast-feeding, the intention of becoming pregnant or not using adequate contraceptive measures
Known or suspected allergy to trial products or related products

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
insulin detemirTreat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection	Drug	Treatment period 1, Treatment period 2
insulin NPHTreat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection	Drug	Treatment period 1, Treatment period 2
insulin aspartTreat-to-target dose tritation (dose adjusted individually), s.c. (under the skin) injection	Drug	Treatment period 1, Treatment period 2

Primary outcome

Total Energy Expenditure, Double-labelled Water Method
Time frame: Weeks 14-16, weeks 30-32
Total energy expenditure (TEE) measured after each treatment period by the double-labelled water (DLW) method. This technique required subjects to label their body water using oral administration of water labelled with 2 stable isotopes (2H218O). The clearance of 2H and 18O was measured over a two week period with daily collections of urine. The difference between the clearance of 2H and 18O is a measure of CO2 production rate. This can be converted to provide a measure of energy expenditure.
Total Energy Expenditure, Dietary Record Method
Time frame: Weeks 14-16, weeks 30-32
The total energy expenditure (TEE) measured after each treatment period by the dietary record method. The calculation of energy balance is accomplished by compiling an accurate record of food intake over a period of time and measuring any changes in body weight that occur during that time. Data from the 7-day food diary was used to calculate TEE.

16 secondary outcomes

Component of Total Energy Expenditure: Resting Energy Expenditure (REE)
Time frame: Week 14, week 30
Component of Total Energy Expenditure: Diet Induced Thermogenesis (DIT)
Time frame: Week 14, week 30
Component of Total Energy Expenditure: Physical Activity Thermogenesis
Time frame: Week 16, week 32
Component of Total Energy Expenditure: Non-exercise Activity Thermogenesis (NEAT)
Time frame: Week 16, week 32
Body Weight
Time frame: Week 16, week 32
Lean Body Mass
Time frame: Week 16, week 32
Fat Mass
Time frame: Week 16, week 32
Waist:Hip Ratio
Time frame: Week 16, week 32
Hormonal Assessment: Adiponectin
Time frame: Week 14, week 30
Hormonal Assessment: Insulin-like Growth Factor-1
Time frame: Week 14, week 30
Hormonal Assessment: Resistin
Time frame: Week 14, week 30
Hormonal Assessment: Leptin
Time frame: Week 14, week 30
Glycosylated Haemoglobin A1c (HbA1c)
Time frame: Week 16, week 32
Fasting Plasma Glucose
Time frame: Week 16, week 32
Hypoglycaemic Episodes
Time frame: Weeks 0-32
Hypoglycaemic Episodes, Diurnal/Nocturnal
Time frame: Weeks 0-32

Results and safety

Results posted to the registry on 4 Aug 2010, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Insulin Detemir First, Then Insulin NPH	12	12
Insulin NPH First, Then Insulin Detemir	11	10

Primary outcome: Total Energy Expenditure, Double-labelled Water Method

Time frame: Weeks 14-16, weeks 30-32. Mean (Standard Deviation). Unit: kcal/day

Measure	Insulin Detemir n = 13	Insulin NPH n = 13
Value	2942.2 (683.9)	3007.2 (649.9)

Population analysed: The analysis was performed on an ITT (Intent-to-Treat) analysis set. The ITT analysis set consisted of all subjects who received at least one post-treatment value of the primary endpoint.

Primary outcome: Total Energy Expenditure, Dietary Record Method

Time frame: Weeks 14-16, weeks 30-32. Mean (Standard Deviation). Unit: kcal/day

Measure	Insulin Detemir n = 21	Insulin NPH n = 21
Value	2017.9 (501.4)	2181.0 (559.8)

16 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events were collected from July 2007 to July 2008.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Insulin Detemir	0 of 23 (0%)	7 of 23 (30.4%)	Not reported
Insulin NPH	0 of 23 (0%)	4 of 23 (17.4%)	Not reported

Limitations and caveats (from the sponsor): This open-label study was terminated prematurely due to 2 unplanned interim analyses having been performed. At this point, only 23 out of the planned 30 patients had been randomised into the study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 10 Mar 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21593292Zachariah S, Sheldon B, Shojaee-Moradie F, Jackson NC, Backhouse K, Johnsen S, Jones RH, Umpleby AM, Russell-Jones DL. Insulin detemir reduces weight gain as a result of reduced food intake in patients with type 1 diabetes. Diabetes Care. 2011 Jul;34(7):1487-91. doi: 10.2337/dc11-0098. Epub 2011 May 18.
Clinical Trials at Novo NordiskLink provided by the sponsor.

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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.

Global Clinical Registry (GCR, 1452) study director

Novo Nordisk A/S

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing insulin detemir, insulin NPH and insulin aspart in people with Diabetes and Diabetes Mellitus, Type 1, run by Novo Nordisk A/S 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 5 inclusion and 6 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: stopped early, as of the sponsor's last update on 10 Mar 2017. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Aug 2010). 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?

Total Energy Expenditure, Double-labelled Water Method (time frame: Weeks 14-16, weeks 30-32). 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?

On the ClinicalTrials.gov record for NCT00509925, 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 10 Mar 2017.