Alzheimer Disease
Conditions
Keywords
Alzheimer's Disease
Brief summary
The trials investigates the changes of cerebral spinal fluid (CSF) soluble alpha-secretase cleaved APP (APPsα) levels under oral therapy with acitretin 30mg daily in patients with mild to moderate Alzheimer's disease (AD).The present study aims to demonstrate an enhancement of the α-secretase activity by acitretin as measured by increased CSF APPSα levels in human AD. Second, the safety and tolerability of acitretin in AD patients should be proven.
Interventions
DRUGAcitretin
30mg per day from Day 1 to Day 28
DRUGPlacebo
Placebo
Sponsors
Alzheimer Forschungsinitiative e.V. (AFI)
K. Lieb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* mild to moderate AD (NINCDS-ADRDA criteria) * Mini-Mental State Examination (MMSE): 27-14 points * Geriatric Depression Scale ≤ 14
Exclusion criteria
* hereditary cognitive impairment * known history of brain injuries * Insufficient German language skills * actual treatment with other potential disease modifying drugs of AD * multimorbidity or significant organ (esp. liver or renal) dysfunction * evidence of Non-AD neurodegenerative disorder (e.g. Parkinson) * contraindication to acitretin such as osteoporosis, hypoalbuminaemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Cerebrospinal Fluid (CSF) Soluble Alpha-clevaed Amyloid Precursor Protein (APPsα) Concentration at Visit 3 Compared to Baseline | baseline and 4 weeks (visit 3) | Values were assessed via Western blotting technique. Normalization was conducted using hSA levels of the individual samples. |
Countries
Germany
Participant flow
Recruitment details
University Medical Centre of the Johannes Gutenberg University, Mainz, and University Medical Centre, Rostock, May 2010 to January 2013
Pre-assignment details
neuropsychiatric testing, general exclusion of e.g. depression or severe diseases affecting the trial
Participants by arm
| Arm | Count |
|---|---|
| Acitretin oral, 30 mg per day, day 1-28
Acitretin: 30mg per day from Day 1 to Day 28 | 11 |
| Placebo oral, day 1-28
Placebo: Placebo | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Acitretin | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 66.9 years STANDARD_DEVIATION 9.6 | 73 years STANDARD_DEVIATION 3.8 | 69.33 years STANDARD_DEVIATION 7.9 |
| MMSE | 20.4 units on a scale STANDARD_DEVIATION 4.2 | 23.9 units on a scale STANDARD_DEVIATION 4.3 | 22.2 units on a scale STANDARD_DEVIATION 4.5 |
| Region of Enrollment Germany | 11 participants | 10 participants | 21 participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 8 / 11 | 5 / 10 |
| serious Total, serious adverse events | 1 / 11 | 0 / 10 |
Outcome results
Primary
Difference in Cerebrospinal Fluid (CSF) Soluble Alpha-clevaed Amyloid Precursor Protein (APPsα) Concentration at Visit 3 Compared to Baseline
Values were assessed via Western blotting technique. Normalization was conducted using hSA levels of the individual samples.
Time frame: baseline and 4 weeks (visit 3)
Population: All patients were included with successful punctation at V1 and V3. For one Acitretin-treated patient not punctation at V3 was obtained (resulting n of 10).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Acitretin | Difference in Cerebrospinal Fluid (CSF) Soluble Alpha-clevaed Amyloid Precursor Protein (APPsα) Concentration at Visit 3 Compared to Baseline | 1.251 fold change (Visit 3/background) | Standard Deviation 0.4528 |
| Placebo | Difference in Cerebrospinal Fluid (CSF) Soluble Alpha-clevaed Amyloid Precursor Protein (APPsα) Concentration at Visit 3 Compared to Baseline | 0.8741 fold change (Visit 3/background) | Standard Deviation 0.2592 |
p-value: 0.034795% CI: [0.03025, 0.7235]t-test, 2 sided