Clinical Trial Results:
MaasFlex: A 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

Trial information Top of page
Trial identification
Sponsor protocol code	NL67170.068.18
Additional study identifiers
ISRCTN number	-
US NCT number	NCT03721874
WHO universal trial number (UTN)	-
Sponsors
Sponsor organisation name	maastricht university
Sponsor organisation address	universiteitssingel 50, maastricht, Netherlands,
Public contact	Project leader, Maastricht University, +31 433881502, p.schrauwen@maastrichtuniversity.nl
Scientific contact	Project leader, Maastricht University, +31 433881502, p.schrauwen@maastrichtuniversity.nl
Paediatric regulatory details
Is trial part of an agreed paediatric investigation plan (PIP)	No
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?	No
Results analysis stage
Analysis stage	Final
Date of interim/final analysis	09 Nov 2022
Is this the analysis of the primary completion data?	Yes
Primary completion date	07 Jul 2021
Global end of trial reached?	Yes
Global end of trial date	07 Jul 2021
Was the trial ended prematurely?	No
General information about the trial
Main objective of the trial	The primary objective is to examine the effects of dapagliflozin on nocturnal substrate oxidation in overweight or obese subjects with disrupted glucose homeostasis but without T2D.
Protection of trial subjects	The Ethics Committee of Maastricht University Medical Center approved the study, which was registered at clinicaltrials.gov (NCT03721874) and conducted conform the declaration of Helsinki
Background therapy	-
Evidence for comparator	-
Actual start date of recruitment	13 Sep 2019
Long term follow-up planned	No
Independent data monitoring committee (IDMC) involvement?	Yes
Population of trial subjects
Number of subjects enrolled per country
Country: Number of subjects enrolled	Netherlands: 14
Worldwide total number of subjects	14
EEA total number of subjects	14
Number of subjects enrolled per age group
In utero	0
Preterm newborn - gestational age < 37 wk	0
Newborns (0-27 days)	0
Infants and toddlers (28 days-23 months)	0
Children (2-11 years)	0
Adolescents (12-17 years)	0
Adults (18-64 years)	4
From 65 to 84 years	10
85 years and over	0

Trial information Top of page

Subject disposition Top of page
Recruitment
Recruitment details	Recruitment of participants will be done in the vicinity of Maastricht by means of posters in public spaces (supermarkets, hospital, pharmacy, general practitioners) and advertisements in local newspapers and on the internet.
Pre-assignment
Screening details	Diagnosis and main criteria for inclusion: Inclusion criteria: − Provision of signed and dated informed consent prior to any study specific procedures. − Men aged ≥ 40 and ≤ 75 years and post-menopausal women (defined as at least 1 year post cessation of menses) aged ≥ 50 and ≤ 75 years. − BMI ≥ 27 and ≤ 38 kg/m2. − Sedentary lifestyle (no
Period 1
Period 1 title	overall period
Is this the baseline period?	Yes
Allocation method	Randomised - controlled
Blinding used	Double blind
Roles blinded	Subject, Investigator, Data analyst
Arms
Are arms mutually exclusive	No
Arm title	placebo
Arm description	-
Arm type	Placebo
Investigational medicinal product name	placebo
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	1 tablet per day
Arm title	dapagliflozin
Arm description	-
Arm type	Active comparator
Investigational medicinal product name	dapagliflozin
Investigational medicinal product code
Other name
Pharmaceutical forms	Tablet
Routes of administration	Oral use
Dosage and administration details	10mg/day in the morning (orally).
Number of subjects in period 1 placebo dapagliflozin Started 14 14 Completed 14 14

Subject disposition Top of page

Baseline characteristics Top of page
Baseline characteristics reporting groups
Reporting group title	overall period
Reporting group description	Male and female individuals between 40 – 75 years and BMI of 27 – 38 kg/m2 without T2DM were eligible for participation. Moreover, the eligible participants should have a sedentary lifestyle and an impaired glucose homeostasis based on one or a combination of criteria including impaired fasting glucose, impaired glucose tolerance, HbA1c ≥ 5.7 and ≤ 6.4% (≥39 and ≤46 mmol/mol) and reduced glucose clearance rate ≤ 360 ml/min/m2 indicating insulin resistance calculated by the Oral Glucose Insulin Sensitivity (OGIS) model.
Reporting group values overall period Total Number of subjects 14 14 Age categorical Units: Subjects     In utero 0 0     Preterm newborn infants (gestational age < 37 wks) 0 0     Newborns (0-27 days) 0 0     Infants and toddlers (28 days-23 months) 0 0     Children (2-11 years) 0 0     Adolescents (12-17 years) 0 0     Adults (18-64 years) 4 4     From 65-84 years 10 10     85 years and over 0 0 Age continuous Units: years     geometric mean (standard deviation) 66.3 ± 6.2 - Gender categorical Units: Subjects     Female 6 6     Male 8 8

Baseline characteristics Top of page

End points Top of page
End points reporting groups
Reporting group title	placebo
Reporting group description	-
Reporting group title	dapagliflozin
Reporting group description	-

End points Top of page

Primary: nocturnal fat oxidation Top of page
End point title	nocturnal fat oxidation
End point description
End point type	Primary
End point timeframe	14 days
End point values placebo dapagliflozin Number of subjects analysed 14 14 Units: g/day     geometric mean (standard deviation) 79.2 ± 4.2 89.5 ± 4.8
Statistical analysis title	cross over comparison
Comparison groups	placebo v dapagliflozin
Number of subjects included in analysis	28
Analysis specification	Post-hoc
Analysis type	superiority
P-value	< 0.05
Method	Wilcoxon (Mann-Whitney)
Confidence interval

Primary: nocturnal fat oxidation Top of page

Primary: 24h fat oxidation Top of page
End point title	24h fat oxidation
End point description
End point type	Primary
End point timeframe	14 days of treatment vs placebo
End point values placebo dapagliflozin Number of subjects analysed 14 14 Units: g/day     geometric mean (standard deviation) 124.3 ± 6 136.1 ± 7.6
Statistical analysis title	comparision placebo vs dapagliflozin
Comparison groups	placebo v dapagliflozin
Number of subjects included in analysis	28
Analysis specification	Post-hoc
Analysis type	superiority
P-value	< 0.05
Method	Wilcoxon (Mann-Whitney)
Confidence interval

Primary: 24h fat oxidation Top of page

Adverse events Top of page
Adverse events information [1]
Timeframe for reporting adverse events	30-4-2019 until 15-07-2001
Adverse event reporting additional description	no adverse events
Assessment type	Non-systematic
Dictionary used for adverse event reporting
Dictionary name	toetsingonline
Dictionary version	1
Frequency threshold for reporting non-serious adverse events: 0%
Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: no adverse events occurred in this small, experimental intervention

Adverse events Top of page

More information Top of page
Substantial protocol amendments (globally)
Were there any global substantial amendments to the protocol? No
Interruptions (globally)
Were there any global interruptions to the trial? No
Limitations and caveats
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
None reported
Online references
http://www.ncbi.nlm.nih.gov/pubmed/36592688

More information Top of page