Diabetes Mellitus, Type 2Phase 4DAPAMAASTNCT03338855

Effects of 5 Weeks Treatment With Dapagliflozin in Type 2 Diabetes Patients on How the Hormone Insulin Acts on Sugar Uptake in Muscles.

A Phase 4 study testing Dapagliflozin in people with Diabetes Mellitus, Type 2 and Skeletal Muscle Insulin Sensitivity, run by AstraZeneca at 1 site in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to investigate the effects of 5 weeks treatment with dapagliflozin in type 2 diabetes patients on how the hormone insulin acts on sugar uptake in muscles. Read more about this study

Who is it for?: Ages 40 to 70 years
Conditions the study is for: Diabetes Mellitus, Type 2, Skeletal Muscle Insulin Sensitivity
What is being tested?: Dapagliflozin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: 1 siteNetherlands
Study dates: 5 Mar 2018to 4 Nov 2019
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 40 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patients are able to provide signed and dated written informed consent prior to any study specific procedures.
Women are post-menopausal (defined as at least 1 year post cessation of menses) and aged ≥ 45 and ≤ 70 years. Males are aged ≥ 40 years and ≤ 70 years. Patients should have suitable veins for cannulation or repeated venipuncture.
Patients are diagnosed with T2DM for at least the last 6 months.
Patients are on no other anti-diabetic drug treatment, or on stable maximum 3000 mg daily dose metformin treatment and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months5. HbA1c levels ≥6.0% (=42 mmol/mol) and ≤9.0% (75 mmol/mol).
Have a body mass index (BMI) ≤ 35 kg/m2.

Who cannot join

Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at third party vendor or at the investigational sites).
Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 3 months or as judged by the Investigator.
History of or presence of any clinically significant disease or disorder including a recent (< 3 months) cardiovascular event which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study or influence the results or the patient's ability to participate in the study.
Clinical diagnosis of Type 1 diabetes, maturity onset diabetes of the young, secondary diabetes or diabetes insipidus.
Unstable/rapidly progressing renal disease or estimated Glomerular Filtration Rate < 60 mL/min (Cockcroft-Gault formula).
Clinically significant out of range values of serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST) or alkaline phosphatase (ALP) in the Investigator's opinion.

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Contraindications to dapagliflozin according to the local label.
Use of antidiabetic drugs other than metformin within 3 months prior to screening.
Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
History of drug abuse or alcohol abuse in the past 12 months.
Any clinically significant abnormalities in clinical chemistry, hematology or urinalysis or other condition the Investigator believes would interfere with the patient's ability to provide informed consent, comply with study instructions, or which might confound the interpretation of the study results or put the patient at undue risk.
Plasma donation within one month of screening or any blood donation/blood loss > 500 mL within 3 months prior to screening or during the study.
Anemia defined as Hemoglobin (Hb) < 115 g/L (7.1 mM) in women and < 120 g/L (7.5 mM) in men.
Use of anti-coagulant treatment such as heparin, warfarin, platelet inhibitors, thrombin and factor X inhibitors.
Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity.
Use of loop diuretics.
Regular smoking and other regular nicotine use.
Any contra-indication to magnetic resonance imaging scanning. These contra-indications include patients with following devices:
Central nervous system aneurysm clip
Implanted neural stimulator
Implanted cardiac pacemaker of defibrillator
Cochlear implant
Metal containing corpora aliena in the eye or brain.
Patients, who do not want to be informed about unexpected medical findings, or do not wish that their physician be informed about coincidental findings, cannot participate in the study.

Trial locations and contacts

1 site in 1 country.

Netherlands1 site

Research Site
Maastricht, 6229 ER

Other trials in Netherlands

About this study

Official title: DAPAMAAST: A Double-blind, Randomized, Phase IV, Mechanistic, Placebo-controlled, Cross-over, Single-center Study to Evaluate the Effects of 5 Weeks Dapagliflozin Treatment on Insulin Sensitivity in Skeletal Muscle in Type 2 Diabetes Mellitus Patients.

The purpose of this study is to investigate the effects of 5 weeks treatment with dapagliflozin in type 2 diabetes patients on how the hormone insulin acts on sugar uptake in muscles.

Read the detailed description

To investigate if dapagliflozin improves skeletal muscle insulin sensitivity expressed as corrected glucose disposal rate (cGDR) in comparison with placebo after 5-week double blind treatment. Insulin sensitivity will be determined using a 2-step euglycemic hyperinsulinemic clamp (EHC) procedure

Conditions: Diabetes Mellitus, Type 2, Skeletal Muscle Insulin Sensitivity
Being tested: Dapagliflozin
Keywords: T2DM, insulin resistance, skeletal muscle, mitochondria, dapagliflozin
Medical subject headings: Diabetes Mellitus, Type 2, Insulin Resistance

What participants receive

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

DapagliflozinDrug
The study consist of 5 weeks treatment period 1, 6-8 weeks wash-out period and 5 weeks treatment period 2.
The patient will be administered dapagliflozin 10 mg during Period 1 or Period 2.

Study groups in NCT03338855
Study group	Role	What they receive
Dapagliflozin	Active comparator	Patients will receive dapagliflozin 10 mg in tablet for a maximum of 40 days based on randomization sequence in Period 1. Patients that received 10 mg dapagliflozin in the first treatment period will receive matching placebo in the second treatment period for a maximum of 40 days. Receives: Drug: Dapagliflozin
Placebo matching to dapagliflozin	Placebo comparator	Patients will receive matching placebo in tablet for a maximum of 40 days based on randomization sequence. Patients who received placebo in the first treatment will receive 10 mg dapagliflozin in the second treatment period, for a maximum of 40 days Receives: Drug: Dapagliflozin

What is being measured

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

Corrected Glucose Disposal Rate (cGDR) Measured as Change in Rate of Disposal (Delta RD) Basal vs High Insulin After 5 Weeks of Treatment
Skeletal muscle insulin sensitivity was measured as cGDR (referred to as delta RD [basal vs high insulin]) using a 2-step 5.5 hour euglycemic hyperinsulinemic clamp (EHC) procedure in combination with infusion of D-glucose (6,6-D2) glucose. Delta RD (basal vs high insulin) was corrected for urinary glucose excretion and measured at the end of Treatment Periods 1 and 2.
Measured: At end (Week 5) of Treatment Periods 1 and 2

Timeline

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

5 Mar 20184 Nov 2019

First posted9 Nov 2017
Study start5 Mar 2018
Primary completion4 Nov 2019
Study completion4 Nov 2019

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 (2)Papers the sponsor has linked to this study.
Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
More trials run by AstraZenecaThe 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: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03338855
Sponsor's protocol ID: D1690C00047
Other IDs: 2016-003991-27, 2016
Acronym: DAPAMAAST
Status last verified: Jan 2021
First submitted: 7 Nov 2017
Last updated: 15 Jan 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

Publications

Op den Kamp YJM, Gemmink A, de Ligt M, Dautzenberg B, Kornips E, Jorgensen JA, Schaart G, Esterline R, Pava DA, Hoeks J, Schrauwen-Hinderling VB, Kersten S, Havekes B, Koves TR, Muoio DM, Hesselink MKC, Oscarsson J, Phielix E, Schrauwen P. Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism. Mol Metab. 2022 Dec;66:101620. doi: 10.1016/j.molmet.2022.101620. Epub 2022 Oct 21.
PubMed 36280113
Op den Kamp YJM, de Ligt M, Dautzenberg B, Kornips E, Esterline R, Hesselink MKC, Hoeks J, Schrauwen-Hinderling VB, Havekes B, Oscarsson J, Phielix E, Schrauwen P. Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial. Diabetes Care. 2021 Jun;44(6):1334-1343. doi: 10.2337/dc20-2887. Epub 2021 Apr 15.
PubMed 33858855

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?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: DAPAMAAST: A Double-blind, Randomized, Phase IV, Mechanistic, Placebo-controlled, Cross-over, Single-center Study to Evaluate the Effects of 5 Weeks Dapagliflozin Treatment on Insulin Sensitivity in Skeletal Muscle in Type 2 Diabetes Mellitus Patients.
ClinicalTrials.gov ID: NCT03338855
Acronym / sponsor ID: DAPAMAAST / D1690C00047
Conditions: Diabetes Mellitus, Type 2, Skeletal Muscle Insulin Sensitivity
Keywords: T2DM, insulin resistance, skeletal muscle, mitochondria, dapagliflozin
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: AstraZenecaIndustry (pharma, biotech, devices)
Study start: 5 Mar 2018 (actual)
Primary completion: 4 Nov 2019 (actual)
Study completion: 4 Nov 2019 (actual)
First posted: 9 Nov 2017 (actual)
Results: Posted 15 Jan 2021

Clinical summary

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

The purpose of this study is to investigate the effects of 5 weeks treatment with dapagliflozin in type 2 diabetes patients on how the hormone insulin acts on sugar uptake in muscles.

Detailed description

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Dapagliflozin	Active comparator	Drug: DapagliflozinPatients will receive dapagliflozin 10 mg in tablet for a maximum of 40 days based on randomization sequence in Period 1. Patients that received 10 mg dapagliflozin in the first treatment period will receive matching placebo in the second treatment period for a maximum of 40 days.
Placebo matching to dapagliflozin	Placebo comparator	Drug: DapagliflozinPatients will receive matching placebo in tablet for a maximum of 40 days based on randomization sequence. Patients who received placebo in the first treatment will receive 10 mg dapagliflozin in the second treatment period, for a maximum of 40 days

Who may qualify

Ages: 40 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patients are able to provide signed and dated written informed consent prior to any study specific procedures.
Women are post-menopausal (defined as at least 1 year post cessation of menses) and aged ≥ 45 and ≤ 70 years. Males are aged ≥ 40 years and ≤ 70 years. Patients should have suitable veins for cannulation or repeated venipuncture.
Patients are diagnosed with T2DM for at least the last 6 months.
Patients are on no other anti-diabetic drug treatment, or on stable maximum 3000 mg daily dose metformin treatment and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months5. HbA1c levels ≥6.0% (=42 mmol/mol) and ≤9.0% (75 mmol/mol).
Have a body mass index (BMI) ≤ 35 kg/m2.

Key exclusion criteria (24 listed)

Involvement in the planning and conduct of the study (applies to both AstraZeneca staff and staff at third party vendor or at the investigational sites).
Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 3 months or as judged by the Investigator.
History of or presence of any clinically significant disease or disorder including a recent (< 3 months) cardiovascular event which, in the opinion of the Investigator, may either put the patient at risk because of participation in the study or influence the results or the patient's ability to participate in the study.
Clinical diagnosis of Type 1 diabetes, maturity onset diabetes of the young, secondary diabetes or diabetes insipidus.
Unstable/rapidly progressing renal disease or estimated Glomerular Filtration Rate < 60 mL/min (Cockcroft-Gault formula).

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
DapagliflozinThe study consist of 5 weeks treatment period 1, 6-8 weeks wash-out period and 5 weeks treatment period 2. The patient will be administered dapagliflozin 10 mg during Period 1 or Period 2.	Drug	Dapagliflozin, Placebo matching to dapagliflozin

Primary outcome

Corrected Glucose Disposal Rate (cGDR) Measured as Change in Rate of Disposal (Delta RD) Basal vs High Insulin After 5 Weeks of Treatment
Time frame: At end (Week 5) of Treatment Periods 1 and 2
Skeletal muscle insulin sensitivity was measured as cGDR (referred to as delta RD [basal vs high insulin]) using a 2-step 5.5 hour euglycemic hyperinsulinemic clamp (EHC) procedure in combination with infusion of D-glucose (6,6-D2) glucose. Delta RD (basal vs high insulin) was corrected for urinary glucose excretion and measured at the end of Treatment Periods 1 and 2.

Results and safety

Results posted to the registry on 15 Jan 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dapagliflozin 10 mg Then Placebo	12	11
Placebo Then Dapagliflozin 10 mg	14	14

Primary outcome: Corrected Glucose Disposal Rate (cGDR) Measured as Change in Rate of Disposal (Delta RD) Basal vs High Insulin After 5 Weeks of Treatment

Time frame: At end (Week 5) of Treatment Periods 1 and 2. Least squares mean (95% Confidence Interval). Unit: micromole/kilogram body weight/minute

Measure	Dapagliflozin 10 mg n = 22	Placebo n = 22
Value	8.523 (5.566 to 11.481)	9.592 (6.634 to 12.549)

Dapagliflozin 10 mg vs Placebo: Least Square (LS) Mean Difference: -1.068 (95% CI -3.183 to 1.047), p = 0.3047, Linear Mixed Effects Model

Population analysed: The evaluable analysis set (clamp) was a subset of the randomized analysis set, consisting of patients who received at least 1 dose of any investigational product. Any patients with important procedure specific protocol deviations regarding the clamp method were excluded.

Adverse events

Time frame: Adverse events (AEs) were reported throughout the treatment period and including the follow-up period. Overall time frame up to a maximum of 19 weeks (including both 5-week treatment periods, 6-8 weeks wash-out and 5-10 days safety follow-up after last dose of study drug).. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dapagliflozin 10mg	0 of 26 (0%)	0 of 26 (0%)	0 of 26
Placebo	0 of 25 (0%)	0 of 25 (0%)	0 of 25

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36280113Op den Kamp YJM, Gemmink A, de Ligt M, Dautzenberg B, Kornips E, Jorgensen JA, Schaart G, Esterline R, Pava DA, Hoeks J, Schrauwen-Hinderling VB, Kersten S, Havekes B, Koves TR, Muoio DM, Hesselink MKC, Oscarsson J, Phielix E, Schrauwen P. Effects of SGLT2 inhibitor dapagliflozin in patients with type 2 diabetes on skeletal muscle cellular metabolism. Mol Metab. 2022 Dec;66:101620. doi: 10.1016/j.molmet.2022.101620. Epub 2022 Oct 21.
Derived from this study: PubMed 33858855Op den Kamp YJM, de Ligt M, Dautzenberg B, Kornips E, Esterline R, Hesselink MKC, Hoeks J, Schrauwen-Hinderling VB, Havekes B, Oscarsson J, Phielix E, Schrauwen P. Effects of the SGLT2 Inhibitor Dapagliflozin on Energy Metabolism in Patients With Type 2 Diabetes: A Randomized, Double-Blind Crossover Trial. Diabetes Care. 2021 Jun;44(6):1334-1343. doi: 10.2337/dc20-2887. Epub 2021 Apr 15.
Redacted CSPLink provided by the sponsor.
Redacted SAPLink 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.

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 4 study testing Dapagliflozin in people with Diabetes Mellitus, Type 2 and Skeletal Muscle Insulin Sensitivity, run by AstraZeneca 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 5 inclusion and 24 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 Jan 2021. 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. 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 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 15 Jan 2021). 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?

Corrected Glucose Disposal Rate (cGDR) Measured as Change in Rate of Disposal (Delta RD) Basal vs High Insulin After 5 Weeks of Treatment (time frame: At end (Week 5) of Treatment Periods 1 and 2). 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 NCT03338855, which also lists 2 linked publications.

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 Jan 2021.