Prediabetic StatePhase 4MaasFlexNCT03721874
Effects of 2 Weeks Treatment With Dapagliflozin in Subjects With an Impaired Glucose Homeostasis on Nocturnal Substrate Oxidation
A Phase 4 study testing Dapagliflozin 10mg in people with Prediabetic State and Substrate Oxidation, run by Maastricht University at 1 site in Netherlands.
Trial summary
The purpose of this study is to investigate the effect of 2 weeks dapagliflozin treatment in individuals with a disrupted glucose homeostasis on the switch between carbohydrate and lipid oxidation during the night Read more about this study
- Who is it for?
- Ages 40 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Prediabetic State, Substrate Oxidation
- What is being tested?
- Dapagliflozin 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- 30 Apr 2019to 29 Jun 2021
- Phase
- Phase 4
- 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 40 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Provision of signed and dated informed consent prior to any study specific procedures.
- Males aged ≥ 40 and ≤ 75 years and post-menopausal women (defined as at least 1 year post cessation of menses) aged ≥ 50 and ≤ 75 years
- Body mass index (BMI) ≥ 27 and ≤ 38 kg/m2.
- Sedentary lifestyle (not more than 3 hours of programmed exercise per week).
- Stable dietary habits.
- Impaired glucose homeostasis based on one or a combination of the following criteria:
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- Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after consumption of the glucose drink during the 2h, 3-point OGTT.
- Impaired Fasting Glucose (IFG): fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l.
- Insulin Resistance: glucose clearance rate ≤ 360 ml/kg/min, as calculated by Oral Glucose Insulin Sensitivity 120 (OGIS120) model based on the 2h, 3-point OGTT.
- HbA1c ≥ 5.7% and ≤ 6.4%.
Who cannot join
- Clinical diagnosis of Type 1 or 2 Diabetes Mellitus.
- Active cardiovascular disease: participants who experienced a heart attack in the last year, or participants who are currently under regular control of a physician for a heart condition.
- Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
- Regular smoking and other regular nicotine use.
- Anaemia.
- Uncontrolled hypertension.
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- Clinically significant out of range values of serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) in the Investigator's opinion.
- Unstable or rapidly progressing renal disease or estimated Glomerular Filtration Rate (eGFR) <60 mL/min (Cockcroft-Gault formula).
- Use of anti-coagulant treatment and other concomitant medication will be evaluated on a case to case basis with a general physician.
- Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity.
- Use of loop diuretics.
- Intake of dietary supplements except multi-vitamins and minerals.
- Alcohol consumption of > 14 drinks per week for women and > 21 drinks per week for men (1 drink = 35 cl beer, 14 cl wine or 4 cl hard liquor).
- Known hypersensitivity to dapagliflozin or any of the excipients of the product.
- For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
- Participation in another biomedical study within 1 month before the screening visit.
- Any contraindication for MRI scanning.
- Participants 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
Maastricht University and Medical Centre
Maastricht, Limburg, 6200 MD
About this study
Official title: MaasFlex: Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study to Evaluate the Effects of 2 Weeks Dapagliflozin Treatment on Nocturnal Substrate Oxidation, Glucose Metabolism and Muscle Mitochondrial Function in Individuals With Impaired Glucose Homeostasis
The purpose of this study is to investigate the effect of 2 weeks dapagliflozin treatment in individuals with a disrupted glucose homeostasis on the switch between carbohydrate and lipid oxidation during the night
Read the detailed description
To investigate if dapagliflozin improves nocturnal substrate oxidation expressed as respiration quotient (RQ) during the sleeping period in comparison with placebo after 2-weeks double blind treatment in subjects with a disrupted glucose homeostasis.
- Conditions
- Prediabetic State, Substrate Oxidation
- Being tested
- Dapagliflozin 10mg, Placebo matching to Dapagliflozin 10 mg
- Keywords
- Dapagliflozin, Disrupted glucose homeostasis, Nocturnal substrate oxidation, Glucose metabolism
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dapagliflozin 10mgDrug
The study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2.
The subject may be administered dapagliflozin 10 mg during Period 1 or Period 2.
Placebo matching to Dapagliflozin 10 mgDrug
The study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2.
The subject may be administered placebo during Period 1 or Period 2.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin 10 mg | Active comparator | Patients will receive dapagliflozin 10 mg in tablet for a maximum of 14 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 14 days. Receives: Drug: Dapagliflozin 10mg |
| Placebo matching to dapagliflozin 10 mg | Placebo comparator | Patients will receive matching placebo in tablet for a maximum of 14 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 14 days Receives: Drug: Placebo matching to Dapagliflozin 10 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period
Comparison of dapagliflozin versus placebo after 14 days of treatment on nightly substrate oxidation as measured by respiratory quotient (VCO2/VO2) during the sleeping period.
Measured: From screening to day 14
Secondary outcomes (8)
Change in morning and late afternoon hepatic glycogen content
Comparison of dapagliflozin versus placebo after 14 days of treatment on hepatic glycogen content determined by non-invasive 13C-MRS (magnetic resonance spectroscopy) in the morning and evening
Measured: 1 hour
Change in 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion
Comparison of dapagliflozin versus placebo after 14 days of treatment on 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion
Measured: 24 hours
Change in 24h plasma markers
Comparison of dapagliflozin versus placebo after 14 days of treatment on 24h plasma markers including plasma glucose, NEFA, total amino acid levels incl BCAA levels, insulin and glucagon
Measured: 24 hours
Change in muscle mitochondrial function
Comparison of dapagliflozin versus placebo after 14 days of treatment on muscle mitochondrial function as determined by high resolution respirometry
Measured: 60 minutes
Change in intrahepatic lipid content and composition
Comparison of dapagliflozin versus placebo after 14 days of treatment on intrahepatic lipid content and composition as determined by non-invasive 1H-MRS (magnetic resonance spectroscopy )
Measured: 45 minutes
Change in intramyocellular lipid content and composition - including acylcarnitine levels
Comparison of dapagliflozin versus placebo after 14 days of treatment on intramyocellular lipid content and composition-including acylcarnitine levels as determined in muscle biopsies
Measured: 45 minutes
Change in muscle glycogen content
Comparison of dapagliflozin versus placebo after 14 days of treatment on muscle glycogen content as determined biochemically in muscle biopsies
Measured: 45 minutes
Change in systolic and diastolic blood pressure
Comparison of dapagliflozin versus placebo after 14 days of treatment on systolic and diastolic blood pressure
Measured: 45 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2018
- Study start30 Apr 2019
- Primary completion29 Jun 2021
- Study completion29 Jun 2021
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 Prediabetic StateStudies 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 4
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Patrick Schrauwen, Maastricht University
- Investigators
- Patrick Schrauwen, Prof. dr., Principal investigator, principle investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03721874
- Sponsor's protocol ID
- NL67170.068.18
- Acronym
- MaasFlex
- Status last verified
- Aug 2021
- First submitted
- 23 Oct 2018
- Last updated
- 19 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Veelen A, Andriessen C, Op den Kamp Y, Erazo-Tapia E, de Ligt M, Mevenkamp J, Jorgensen JA, Moonen-Kornips E, Schaart G, Esterline R, Havekes B, Oscarsson J, Schrauwen-Hinderling VB, Phielix E, Schrauwen P. Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial. Metabolism. 2023 Mar;140:155396. doi: 10.1016/j.metabol.2022.155396. Epub 2022 Dec 30.
PubMed 36592688
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MaasFlex: Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study to Evaluate the Effects of 2 Weeks Dapagliflozin Treatment on Nocturnal Substrate Oxidation, Glucose Metabolism and Muscle Mitochondrial Function in Individuals With Impaired Glucose Homeostasis
- ClinicalTrials.gov ID
- NCT03721874
- Acronym / sponsor ID
- MaasFlex / NL67170.068.18
- Conditions
- Prediabetic State, Substrate Oxidation
- Keywords
- Dapagliflozin, Disrupted glucose homeostasis, Nocturnal substrate oxidation, Glucose metabolism
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- 30 Apr 2019 (actual)
- Primary completion
- 29 Jun 2021 (actual)
- Study completion
- 29 Jun 2021 (actual)
- First posted
- 26 Oct 2018 (actual)
- 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.
The purpose of this study is to investigate the effect of 2 weeks dapagliflozin treatment in individuals with a disrupted glucose homeostasis on the switch between carbohydrate and lipid oxidation during the night
Detailed description
To investigate if dapagliflozin improves nocturnal substrate oxidation expressed as respiration quotient (RQ) during the sleeping period in comparison with placebo after 2-weeks double blind treatment in subjects with a disrupted glucose homeostasis.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin 10 mg | Active comparator | Drug: Dapagliflozin 10mgPatients will receive dapagliflozin 10 mg in tablet for a maximum of 14 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 14 days. |
| Placebo matching to dapagliflozin 10 mg | Placebo comparator | Drug: Placebo matching to Dapagliflozin 10 mgPatients will receive matching placebo in tablet for a maximum of 14 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 14 days |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Provision of signed and dated informed consent prior to any study specific procedures.
- Males aged ≥ 40 and ≤ 75 years and post-menopausal women (defined as at least 1 year post cessation of menses) aged ≥ 50 and ≤ 75 years
- Body mass index (BMI) ≥ 27 and ≤ 38 kg/m2.
- Sedentary lifestyle (not more than 3 hours of programmed exercise per week).
- Stable dietary habits.
Key exclusion criteria (18 listed)
- Clinical diagnosis of Type 1 or 2 Diabetes Mellitus.
- Active cardiovascular disease: participants who experienced a heart attack in the last year, or participants who are currently under regular control of a physician for a heart condition.
- Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
- Regular smoking and other regular nicotine use.
- Anaemia.
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 |
|---|---|---|
| Dapagliflozin 10mgThe study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2. The subject may be administered dapagliflozin 10 mg during Period 1 or Period 2. | Drug | Dapagliflozin 10 mg |
| Placebo matching to Dapagliflozin 10 mgThe study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2. The subject may be administered placebo during Period 1 or Period 2. | Drug | Placebo matching to dapagliflozin 10 mg |
Primary outcome
Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period
Time frame: From screening to day 14
Comparison of dapagliflozin versus placebo after 14 days of treatment on nightly substrate oxidation as measured by respiratory quotient (VCO2/VO2) during the sleeping period.
8 secondary outcomes
Change in morning and late afternoon hepatic glycogen content
Time frame: 1 hour
Change in 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion
Time frame: 24 hours
Change in 24h plasma markers
Time frame: 24 hours
Change in muscle mitochondrial function
Time frame: 60 minutes
Change in intrahepatic lipid content and composition
Time frame: 45 minutes
Change in intramyocellular lipid content and composition - including acylcarnitine levels
Time frame: 45 minutes
Change in muscle glycogen content
Time frame: 45 minutes
Change in systolic and diastolic blood pressure
Time frame: 45 minutes
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 19 Aug 2021.
- Derived from this study: PubMed 36592688Veelen A, Andriessen C, Op den Kamp Y, Erazo-Tapia E, de Ligt M, Mevenkamp J, Jorgensen JA, Moonen-Kornips E, Schaart G, Esterline R, Havekes B, Oscarsson J, Schrauwen-Hinderling VB, Phielix E, Schrauwen P. Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial. Metabolism. 2023 Mar;140:155396. doi: 10.1016/j.metabol.2022.155396. Epub 2022 Dec 30.
- Individual participant dataSharing planned: No
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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.
Patrick Schrauwen, Prof. dr. principal investigator
principle investigator
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 10mg in people with Prediabetic State and Substrate Oxidation, run by Maastricht University 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 10 inclusion and 18 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 19 Aug 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?
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?
Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period (time frame: From screening to day 14). 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 NCT03721874, 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 19 Aug 2021.