Clinical Trial Results:
pilot study to investigate the effect of e.-coli-nissle as probiotic adjuvant to antidiabetic standard care in patients with diabetic mellitus type 2
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Summary
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EudraCT number |
2014-000936-40 |
Trial protocol |
DE |
Global end of trial date |
15 Dec 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Nov 2021
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First version publication date |
27 Nov 2021
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Other versions |
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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 |
PUNiDIA-2014
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GWT-TUD GmbH
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Sponsor organisation address |
Freiberger Str. 33, Dresden, Germany, 01067
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Public contact |
Medical Consulting, GWT-TUD GmbH, 0049 35125933100, medical.consulting@g-wt.de
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Scientific contact |
Medical Consulting, GWT-TUD GmbH, +49 35125933100, medical.consulting@g-wt.de
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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 |
28 Feb 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Dec 2015
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Dec 2015
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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 |
Decrease in HbA1c levels within baseline and end of treatment
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Protection of trial subjects |
The conduct of this study was in compliance with the Good Clinical Practice Guidelines and under the guiding principles detailed in the Declaration of Helsinki. The study was also be carried out in keeping with applicable local law(s) and regulation(s).
Mutaflor® contains the bacterium E. coli strain Nissle 1917 (EcN) as active ingredient and is approved under the German Drug Law (AMG). From its use over decades (approx. 90 years) and results of clinical studies, it is known that EcN is very well tolerated in doses of up to 1 x 5 ml/day as a suspension.
Risks associated with additional blood sampling were local hematoma or, very rarely, malpuncture with injury to arteries or nerves. These risks were considered to be low, as the examinations were performed by trained and qualified personnel.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Jul 2014
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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 |
Germany: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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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) |
2
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
The clinical trial was conducted between September 2014 and December 2015, a total of 18 patients were screened at the Carus General Practitioner's Office at Dresden University Hospital. The study was conducted and completed according to protocol. | |||||||||
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Pre-assignment
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Screening details |
In total 10 patients were included. The first 5 patients received 1 ml of EcN suspension daily for the entire 24-week treatment period. Based on the first interim results, the dose was increased for the next 5 patients included. They took 5 ml of EcN suspension 5 ml of EcN suspension over the entire treatment period. | |||||||||
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Period 1
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Period 1 title |
Treatment phase (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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1 ml Suspension | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Escherichia coli strain Nissle 1917
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Investigational medicinal product code |
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Other name |
Mutaflor®
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
1 ml of E. coli Nissle 1917 suspension per day over a period of 24 weeks
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Arm title
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5 ml Suspension | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Escherichia coli strain Nissle 1917
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Investigational medicinal product code |
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Other name |
Mutaflor®
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
5 ml of E. coli Nissle 1917 suspension per day over a period of 24 weeks
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Baseline characteristics reporting groups
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Reporting group title |
1 ml Suspension
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
5 ml Suspension
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
1 ml Suspension
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Reporting group description |
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Reporting group title |
5 ml Suspension
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Reporting group description |
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End point title |
Decrease of the HbA1c | ||||||||||||
End point description |
Change in HbA1c between baseline (visit 2) and EoT (visit 4).
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End point type |
Primary
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End point timeframe |
24 weeks
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Statistical analysis title |
Efficacy analysis | ||||||||||||
Statistical analysis description |
The change in HbA1c between baseline and visit 4 as the primary study endpoint was analyzed using descriptive parameters and progress charts. All descriptive results were made available to the study management for interpretation in order to include group characteristics as well as individual progressions for the evaluation of effectiveness.
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Comparison groups |
1 ml Suspension v 5 ml Suspension
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Number of subjects included in analysis |
10
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||
Method |
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Parameter type |
Median difference (final values) | ||||||||||||
Point estimate |
-0.2
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Confidence interval |
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level |
95% | ||||||||||||
sides |
1-sided
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lower limit |
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upper limit |
0 | ||||||||||||
Variability estimate |
Standard deviation
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| Notes [1] - Using these estimators, the study management was able to assess whether adjuvant therapy with E. coli Nissle resulted in an improvement of at least 0.1% or 0.2% in HbA1c at otherwise unchanged standard antidiabetic therapy. The expected decrease in HbA1c of at least 0.1 and 0.2 % was not achieved in both groups of patients. |
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Adverse events information
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Timeframe for reporting adverse events |
from week 0 (visit 1) until week 24 (visit 4)
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
Overall reported AEs
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Reporting group description |
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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. | |||
| None reported | |||
