Clinical Trial Results:
The effect of sitagliptin on brown adipose tissue and whole-body metabolism in overweight pre-diabetic men
Summary
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EudraCT number |
2014-003532-39 |
Trial protocol |
NL |
Global end of trial date |
01 Jan 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Dec 2021
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First version publication date |
13 Dec 2021
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Other versions |
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Summary report(s) |
Nahon et al, Diabetologia 2018 |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
SitaBAT01
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02294084 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Leiden University Medical Center
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Sponsor organisation address |
Albinusdreef 2, Leiden, Netherlands, 2333 ZA
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Public contact |
dr MR Boon (m.r.boon@lumc.nl), Leiden University Medical Center, 0031 648126425, m.r.boon@lumc.nl
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Scientific contact |
dr MR Boon (m.r.boon@lumc.nl), Leiden University Medical Center, 0031 648126425, m.r.boon@lumc.nl
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
02 Jul 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Dec 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
01 Jan 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The main object of the trial is to evaluate the effect of sitagliptin treatment on BAT activity in overweight, pre-diabetic subjects.
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Protection of trial subjects |
Subjects were placed in a comfortable room and at any time, a medical doctor was present during the study days to make subjects feel safe and comfortable.
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Background therapy |
Half of the subjects received the approved medicine Sitagliptin (100 mg/day) for 12 weeks and half of the subjects a placebo. Sitagliptin is a DPP4 inhibitor that increases the action of the intestinal hormone GLP-1. This medicine is currently used in the treatment of type 2 diabetes mellitus. | ||
Evidence for comparator |
The dipeptidyl peptidase-4 (DPP4) inhibitor sitagliptin, which enhances the bioavailability of incretin hormones, improves both glucose tolerance and lipid metabolism in individuals with type 2 diabetes, thereby targeting both microvascular and macrovascular complications. The precise mechanism by which sitagliptin exerts these positive metabolic effects remains largely unknown and in the current study, we aimed to study whether it worked by enhancing activity of metabolically active brown adipose tissue. | ||
Actual start date of recruitment |
01 Jan 2015
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Netherlands: 30
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Worldwide total number of subjects |
30
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EEA total number of subjects |
30
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
30
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
Subjects were recruited from approximately June 2015 until October 2016. Recruitment was done via advertisements. | ||||||||||||
Pre-assignment
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Screening details |
We performed a thorough medical history and physical examination. Furthermore, we performed anthropometric measurements and assessed a venous blood sample to exclude the presence of type 2 diabetes, liver and kidney disease. In addition, we performed an OGTT. | ||||||||||||
Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst | ||||||||||||
Blinding implementation details |
On forehand, an unblinded pharmacist set up a list in which each study subject number was coupled to a box number. All boxes (sitagliptin and placebo) were labeled together with a component ID list (this contained the information which box holded the placebo or sitagliptin). The pharmacy then gave out the boxes according to the randomisation list. Therefore, the study was conducted double blind.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Sitagliptin | ||||||||||||
Arm description |
Sitagliptin (100 mg/day) treatment | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Sitagliptin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
100 mg/day per os, for 12 weeks in total
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Arm title
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Placebo | ||||||||||||
Arm description |
Placebo treatment | ||||||||||||
Arm type |
Placebo | ||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo tablet 100 mg, in total 12 weeks treatment
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Baseline characteristics reporting groups
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Reporting group title |
Sitagliptin
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Reporting group description |
Sitagliptin (100 mg/day) treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo treatment | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Sitagliptin
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Reporting group description |
Sitagliptin (100 mg/day) treatment | ||
Reporting group title |
Placebo
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Reporting group description |
Placebo treatment |
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End point title |
Change in brown adipose tissue activity | ||||||||||||
End point description |
Before and after 12 weeks of sitagliptin or placebo treatment brown adipose tissue volume and activity were measured using PET-CT scan.
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End point type |
Primary
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End point timeframe |
12 weeks
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Attachments |
Overview effects brown fat |
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Statistical analysis title |
Statistical analysis | ||||||||||||
Statistical analysis description |
Mixed model analyses with treatment and occasion as fixed effects and subject specific deviances from the mean as random effects were used to assess the effect of the treatment.
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Comparison groups |
Sitagliptin v Placebo
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority [1] | ||||||||||||
P-value |
< 0.05 [2] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.8 | ||||||||||||
upper limit |
2.1 | ||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
0.1
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Notes [1] - we compared whether sitagliptin was superior to placebo treatment in inducing brown adipose tissue activation [2] - We considered a P-vlaue < 0.05 as statistically significant |
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End point title |
Change in brown adipose tissue volume | ||||||||||||
End point description |
Brown adipose tissue volume was measured in mL and was assessed via 18F-FDG PET-CT scan
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End point type |
Primary
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End point timeframe |
Before and after 12 weeks of treatment with sitagliptin and placebo effects on brown adipose tissue volume were measured.
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Attachments |
Overview effects brown fat |
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Statistical analysis title |
Statistical analysis | ||||||||||||
Statistical analysis description |
Mixed model analyses with treatment and occasion as fixed effects and subject specific deviances from the mean as random effects were used to assess the effect of the treatment
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Comparison groups |
Sitagliptin v Placebo
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Number of subjects included in analysis |
30
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
< 0.05 [4] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
20
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
12 | ||||||||||||
upper limit |
33 | ||||||||||||
Variability estimate |
Standard deviation
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Dispersion value |
12
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Notes [3] - We assessed whether sitagliptin was superior to enhance brown adipose tissue volume compared with placebo [4] - We considered a P-value < 0.05 as statistically significant. |
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End point title |
Change in incremental glucose during OGTT | ||||||||||||
End point description |
see above
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End point type |
Secondary
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End point timeframe |
An OGTT was performed before and 12 weeks after sitagliptin treatment. From this OGTT, amongst others, an incremental glucose was assessed.
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Statistical analysis title |
AUC of the incremental glucose (OGTT) | ||||||||||||
Statistical analysis description |
Mixed model analysis was used to assess differences in the AUC of the incremental glucose during OGTT
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Comparison groups |
Placebo v Sitagliptin
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Number of subjects included in analysis |
29
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Analysis specification |
Pre-specified
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Analysis type |
equivalence [5] | ||||||||||||
P-value |
< 0.003 [6] | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
2.1
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
1.2 | ||||||||||||
upper limit |
4.1 | ||||||||||||
Notes [5] - Mixed model analysis was used [6] - We also assessed the P-value for the difference between t=0 and t=12 weeks, this was also P<0.003 |
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Adverse events information
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Timeframe for reporting adverse events |
during the 12 week treatment period we assess adverse events.
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Adverse event reporting additional description |
We assessed this by weekly calling the study subjects.
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Assessment type |
Systematic | |||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
via sponsor | |||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
sitagliptin
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Reporting group description |
subjects who received sitagliptin treatment (100 mg/day) | |||||||||||||||||||||
Reporting group title |
placebo
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Reporting group description |
subjects that received placebo treatment for 12 weeks | |||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
In this overview, we only report on the effects on brown adipose tissue. The very interesting effects on secondary parameters (glucose and lipid metabolism) can be read in the manuscript that is attached. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/30145664 |