E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Early Alzheimer´s dementia (eAD), type 2 diabetes mellitus with amnestic mild cognitive impairment (T2D-aMCI), healthy controls (Co) |
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E.1.1.1 | Medical condition in easily understood language |
Early Alzheimer´s dementia, type 2 diabetes mellitus with amnestic mild cognitive impairment, healthy controls |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10012271 |
E.1.2 | Term | Dementia Alzheimer's type |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
It should be proofed that the intranasal application of the IMP is an enhancement for patients with early Alzheimer's dementia concerning their declarative recall. |
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E.2.2 | Secondary objectives of the trial |
Investigate the effect of intranasal Inuslin to
1) advanced cognitive performance parameter
2) the time interval that is experiencing a possible improvement in cognitive performance
3) neuronal and glial metabolites measured by proton magnetic resonance spectroscopy (1H MRS)
4) food intake, body weight and Body fat
5) How long is the memory performance effected by intranasal inulin in patients with early Alzheimer's dementia, in pts with type 2 diabetes mellitus and in control subjects at the follow-up investigation? What implications can be found in the follow-up examination?
6) Effect of intranasal insulin on the Neuroproteomics and the Neurometabolom compared to the baseline examination. Representation of possible pathogenic mechanisms for the identification of targets for new therapeutic approaches. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
group (1) Early Alzheimer´s dementia (eAD), Mini Mental State Examination (MMSE) score 18-25, aged 65 to 85 years of age; AD-indicative biomarker pattern according to cerebrospinal fluid-based neurochemical dementia diagnostics (CSF-NDD); Clinical Dementia Rating score 1.0; stable treatment with cholinesterase inhibitors for at least 3 months;
group (2) Type 2 diabetes mellitus and with amnestic mild cognitive impairment (T2D-aMCI), 65 to 85 years of age, HbA1c 6.5-8.0% on unchanged antidiabetic therapy during the foregoing 4 weeks, duration of diabetes > 5 years; MCI according to the common network criteria; normal activities of daily living, amnestic MCI according to impaired objective memory function as assessed by CERAD word list delayed recall and WMS-R logical memory, CDR=0.5
group (3) non-MCI, non-dementia controls (Co), aged 65 to 85 years
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E.4 | Principal exclusion criteria |
ad (1): Moderate to severe AD (MMSE < 18; CDR < 1.0); antidementive drug therapy other than cholinesterase inhibitors, other neurodegenerative diseases (e.g. Parkinson´s disease; dementia with Lewy bodies, frontotemporal lobe dementia), diabetes mellitus, abuse or addiction to psychoactive compounds (e.g. alcohol, benzodiazepines)
ad (2) T2D with frequent dysglycemic episodes (severe hypoglycemia or coma diabeticum during the foregoing 3 month, HbA1c > 8.0%), concomitant neurodegenerative diseases, otherwise the exclusion criteria apply which are valid for eAD (1);
Ad (3): MCI, dementia, diabetes mellitus, neurodegenerative diseases; otherwise the exclusion criteria apply which are valid for eAD (1) and T2D-aMCI (2), accept contraindications for CSF-based neurochemical dementia diagnostics (CSF-NDD), since CSF-NDD will not be performed in controls.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary outcome is the change in delayed recall from baseline to performance after 8 weeks of intranasal treatment with rapid-acting insulin analogue insulin aspartate (ASP-I) or placebo. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Visit 3,5 and 9 (declarative immediate recall)
Visit 4,6 and 10 (declarative delayed recall) |
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E.5.2 | Secondary end point(s) |
1. Declarative immediate recall after 8 weeks treatment with IMP
2. Changes in advanced cognitive ability
3. Changes measured via MR-spectroscopy
4. Changes in blood-based biochemic parameters and physical parameters
5. Changes in blood-based biochemic parameters which are relevant concerning safety of the IMP
6. Planed neuroproteomic analyse
7. Neurometabolic profile of the liquor
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 8 weeks after treatment with IMP
2. visit 4,6,8,10,12 and 14
3. visit 3,10 and 14
4. see protocol table 1
5. see protocol table 1
6. screening and visit 10
7. screening and visit 10 |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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last visit of the last subject undergoing the trial |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 18 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |