Mild Cognitive Impairment Due to Alzheimer's Disease
Conditions
Brief summary
Patients with mild cognitive impairment due to Alzheimer's disease (MCI due to AD) are at high risk to develop Alzheimer´s dementia. The therapeutic agent Contraloid has the potential to influence the chronic neurodegenerative process of AD. As Contraloid was so far only administered to healthy subjects, the rational of the proposed study is first to collect safety data in patients diagnosed with MCI due to AD, as the absorption, distribution, metabolism and excretion processes may be altered by disease, aging, comorbidities and concomitant drug therapies. Additionally, the design of a subsequent phase II study will be based on the data of this study. The results of the exploratory analyses will enable power calculations and the identification of the most useful and reliable biomarkers for the subsequent proof of concept phase II study.
Interventions
DRUGContraloid acetate
Oral administration of drug substance capsules
DRUGPlacebo
Oral administration of placebo without any exipients.
Sponsors
Berlin Institute of Health
Federal Agency for Disruptive Innovation - SPRIN-D
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients diagnosed with MCI due to AD according to DSM-V 2. Age between 50 and 80 years (male and female) 3. MMSE score 22-30 4. Written informed consent (according AMG §40 (1) 3b) 5. Level of Aβ-oligomers: mind. 1fM 6. CSF according to diagnosis (p-tau \> 62 pg/ml, total CSF Aβ 1-42/1-40 ratio ≤ 0.055) 7. 3 months prior to screening stable medication 8. Females without childbearing potential
Exclusion criteria
1. History of seizures 2. History of stroke or TIA 3. Unstable medical, neurological or psychiatric condition 4. Current treatment with one of the following substances: * Typical antipsychotic or neuroleptic medication within 6 months of screening * Anti-coagulation medications within 3 months of screening * Chronic use of opiates or opioids (including long-acting opioid medication) within 3 months of screening * Stimulant medications (amphetamine, methylphenidate preparations, or modafinil) within 1 month of screening and throughout the study * Chronic use of benzodiazepines, barbiturates, or hypnotics from 3 months before screening 5. Persons who are legally detained in an official institution 6. Persons who may be dependent on the sponsor, the investigator or the trial site 7. Persons without caregiver 8. Participation in other clinical trials according to AMG (1 month before the time of this trial) 9. Persons showing EEG abnormalities
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0 | From baseline (day 1) to follow-up (day 56) | Number of Adverse Events |
| Safety: Number of Participants with abnormal ECG values | From baseline (day 1) to follow-up (day 56) | ECG |
| Safety: Number of Participants with abnormal laboratory values (urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST) | From baseline (day 1) to follow-up (day 56) | Laboratory values: urinalysis, CBC, Quick, PTT, Creatinine, CK, CRP, ALT, AST |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics: Peak Plasma Concentration (Cmax) | pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 | Cmax in plasma |
| Pharmacokinetics: The time at which Cmax is observed (Tmax) | pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 | Tmax in plasma |
| Pharmacokinetics: Terminal elimination half-life (t1/2) in plasma | pre-dose and 15 min, 1 hour, 2 hours, 4 hours post-dose at day 1 and day 28 | t1/2 in plasma |
Other
| Measure | Time frame | Description |
|---|---|---|
| Efficacy optional: Change of biomarkers in feces | Baseline to end of treatment (day 28) to follow-up (day 56) | Biomarkers: p-tau, t-tau, NFL, Aβ 1-40, Aβ 1-42 and Aβ and tau oligomers |
| Efficacy: Change of biomarkers in plasma | Baseline to end of treatment (day 28) to follow-up (day 56) | Biomarkers: p-tau, t-tau, NFL, Aβ 1-40, Aβ 1-42 and Aβ and tau oligomers |
| Efficacy: Change in CERAD+ test battery scores | Baseline to end of treatment (day 28) to follow-up (day 56) | — |
| Efficacy: Change in CDR-Sum of boxes | Baseline to end of treatment (day 28) to follow-up (day 56) | — |
| Efficacy: Change of biomarkers in CSF | Baseline to end of treatment (day 28) to follow-up (day 56) | Biomarkers: p-tau, t-tau, NFL, Aβ 1-40, Aβ 1-42 and Aβ and tau oligomers |
Countries
Germany
Outcome results
None listed