Clinical Trial Results:
Prospective, open-label, two-arm, parallel-group, single center phase IV clinical trial to evaluate the diagnostic value of a Gadobutrol enhanced dynamic susceptibility perfusion MRI (DSC-MRP) and a non contrast arterial spin labeling perfusion MRI (ASL-MRP) in subjects with minor cognitive impairment or minor Alzheimer's disease compared to age matched mentally healthy subjects
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Summary
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EudraCT number |
2012-001583-29 |
Trial protocol |
DE |
Global end of trial date |
05 Oct 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
03 May 2020
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First version publication date |
03 May 2020
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Other versions |
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Summary report(s) |
Synopsis |
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 |
Er-02-Perf-AD
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
EudraCT: 2012-001583-29 | ||
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Sponsors
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Sponsor organisation name |
Universitätsklinikum Erlangen
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Sponsor organisation address |
Schwabachanlage 6, Erlangen, Germany, 91054
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Public contact |
Prof. Dr. Arnd Dörfler, University of Erlangen, 49 091318539388, neuroradiologie@uk-erlangen.de
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Scientific contact |
Prof. Dr. Arnd Dörfler, University of Erlangen, 49 091318539388, neuroradiologie@uk-erlangen.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 |
05 Oct 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
01 Jan 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Oct 2016
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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 |
To compare the robustness of Gadobutrol enhanced DSC-MRP with spin-labeling perfusion studies in subjects with MCI and minor Alzheimer´s disease (AD)
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Protection of trial subjects |
There are no measures necessary for the examination.
For minimise distress they get earphones for sound noising. If patients are scared or had claustrophobic the can get sedatives.
We monitor patients with video and they all have a button for emergency cases
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Background therapy |
no background therapy | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Jul 2012
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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: 65
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Worldwide total number of subjects |
65
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EEA total number of subjects |
65
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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) |
39
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From 65 to 84 years |
26
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85 years and over |
0
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Recruitment
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Recruitment details |
The recruitment started on November 2012 and ended on January 2016. The Recruitment was only at university hospital erlangen at the department of neuroradiology | |||||||||
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Pre-assignment
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Screening details |
Subjects with clinical diagnosed minor congnitive impairment or minor Alzheimers Disease based on neuropsychological testing and the MMSE score. Main criterias was adult subjects, age >45 years, Subjects with symptoms of MCI or minor AD referred for diagnostic work-up with MRI - or mentally healthy control subjects in the same age range | |||||||||
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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 |
Not applicable
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Blinding used |
Not blinded | |||||||||
Blinding implementation details |
no blinding done
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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ARM 1 | |||||||||
Arm description |
40 Subjects with MCI or minor AD will undergo a single MRI study with two types of perfusion measurements: Gadobutrol enhanced DSC-MRP and ASL-MRP. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Gadovist
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Investigational medicinal product code |
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Other name |
Gadobutrol
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Gadovist® (Gadobutrol, 1.0 M gadolinium chelate, Bayer Healthcare)
contrast agent is given intravenous with a dose of 0,1mmol/kg of BW via injector.
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Arm title
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ARM 2 | |||||||||
Arm description |
Arm 2: 10 mentally healthy subjects will serve as a reference and will undergo a single MRI study with two types of perfusion measurements: Gadobutrol enhanced DSC-MRP and ASL-MRP. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Gadovist
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Investigational medicinal product code |
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Other name |
Gadobutrol
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
Gadovist® (Gadobutrol, 1.0 M gadolinium chelate, Bayer Healthcare)
contrast agent is given intravenous with a dose of 0,1mmol/kg of BW via injector.
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Baseline characteristics reporting groups
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Reporting group title |
overall trial
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Demographics
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
33 males (48.5%) and 35 females (51.5%) were enrolled in this study. The mean age was 64 years, the mean weight 79.67kg and the mean height 169.1cm.
All subjects in the study were of Caucasian origin.
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Subject analysis set title |
Medical History
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All relevant medical history was recorded at the screening visit. Table 7 provides the summary of patient`s medical history classified by involved System Organ Class (SOC) and MedDRA preferred term (PT) for the population.
10 (14.7%) subjects had a medical history of Cerebral endovascular aneurysm repair in the study. That is because for the reference group patients were randomized who became a control MRI.
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Subject analysis set title |
Baseline findings
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All relevant Baseline findings were recorded at the screening visit. Table 8 provides the summary of patient`s Baseline findings classified by involved System Organ Class (SOC) and MedDRA preferred term (PT) for the population.
40 (58.8%) and 30 (44.1%) subjects had a Baseline finding of Cognitive disorder and Hypertension in the study.
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Subject analysis set title |
MMSE
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All subjects will undergo a detailed neuropsychological testing and Mini-Mental Score Examination (MMSE) before entering the study protocol. The mean MMSE for all patients was 26.8, for only the subjects 25.6 and for the control group 29.5. Table 10 provides the MMSE scores.
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Subject analysis set title |
Analysis of Efficacy
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Averaged values for cortex, deep white matter and hippocampus in both hemispheres are presented. DSC-MRP results in a more robust perfusion assessment compared to ASL-MRP. There was no statistical significant difference when comparing image quality of DSC-MRP to ASL-MRP (p > 0.12).
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End points reporting groups
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Reporting group title |
ARM 1
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Reporting group description |
40 Subjects with MCI or minor AD will undergo a single MRI study with two types of perfusion measurements: Gadobutrol enhanced DSC-MRP and ASL-MRP. | ||
Reporting group title |
ARM 2
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Reporting group description |
Arm 2: 10 mentally healthy subjects will serve as a reference and will undergo a single MRI study with two types of perfusion measurements: Gadobutrol enhanced DSC-MRP and ASL-MRP. | ||
Subject analysis set title |
Demographics
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
33 males (48.5%) and 35 females (51.5%) were enrolled in this study. The mean age was 64 years, the mean weight 79.67kg and the mean height 169.1cm.
All subjects in the study were of Caucasian origin.
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Subject analysis set title |
Medical History
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All relevant medical history was recorded at the screening visit. Table 7 provides the summary of patient`s medical history classified by involved System Organ Class (SOC) and MedDRA preferred term (PT) for the population.
10 (14.7%) subjects had a medical history of Cerebral endovascular aneurysm repair in the study. That is because for the reference group patients were randomized who became a control MRI.
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Subject analysis set title |
Baseline findings
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All relevant Baseline findings were recorded at the screening visit. Table 8 provides the summary of patient`s Baseline findings classified by involved System Organ Class (SOC) and MedDRA preferred term (PT) for the population.
40 (58.8%) and 30 (44.1%) subjects had a Baseline finding of Cognitive disorder and Hypertension in the study.
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Subject analysis set title |
MMSE
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All subjects will undergo a detailed neuropsychological testing and Mini-Mental Score Examination (MMSE) before entering the study protocol. The mean MMSE for all patients was 26.8, for only the subjects 25.6 and for the control group 29.5. Table 10 provides the MMSE scores.
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Subject analysis set title |
Analysis of Efficacy
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Averaged values for cortex, deep white matter and hippocampus in both hemispheres are presented. DSC-MRP results in a more robust perfusion assessment compared to ASL-MRP. There was no statistical significant difference when comparing image quality of DSC-MRP to ASL-MRP (p > 0.12).
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End point title |
Image quality | ||||||||||||||||||
End point description |
As primary efficacy endpoint, an overall assessment of image quality will be performed by the blinded readers for both DSC- and ASL-MRP images combined:
DSC-MRP better than ASL-MRP
Both equal
ASL-MRP better than DSC-MRP
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End point type |
Primary
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End point timeframe |
The period of observation extends from the time when the informed consent form was signed until 30 min after last administration of IP(s)
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Statistical analysis title |
Primary Efficacy | ||||||||||||||||||
Statistical analysis description |
Three populations were considered for the analyses: the modified intention-to-treat (MITT) the per-protocol (PP) and the safety population. All efficacy endpoints were analyzed for the MITT and PP population of which the MITT population analysis was the primary and PP was the secondary analyses sets and all safety endpoints was analyzed for the safety population
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Comparison groups |
ARM 1 v ARM 2
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Number of subjects included in analysis |
65
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||
P-value |
< 0.05 [1] | ||||||||||||||||||
Method |
ANOVA | ||||||||||||||||||
Confidence interval |
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| Notes [1] - statistically significant. |
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Adverse events information
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Timeframe for reporting adverse events |
The period of observation for an AE extends from the time when the informed consent form was signed until 30 min after last administration of IP(s)
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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 |
19
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Reporting groups
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Reporting group title |
Headache
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||
Reporting group title |
Vertigo
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Reporting group description |
Vertigo was considered not to be related to study drug | ||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||
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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. | |||
| 65 patients were in the PP population as 3 patients were drop-outs. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/31617743 |
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