Impact of CHOlinergic Stimulation on COgnitive and MOtor Functions and Brain Activity in Elderly Volunteers (CHOCOMO) - a randomised, placebo-controlled trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Carl Von Ossietzky Universitaet Oldenburg

Participant type

Healthy volunteers

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

17 Feb 2025 → ongoing

Decision date (initial)

2024-07-16

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Deutsche Forschungsgemeinschaft (DFG)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Others

To compare the effects of an increase of acetylcholine levels by administration of a single 5 mg acute dose of the cholinerase inhibitor donepezil versus placebo on cognitive-motor Dual-task costs in the elderly

Secondary objectives 2

1. To compare the effects of donepezil versus placebo on brain mechanisms (neuronal activity) during task performance
2. To compare the effects of donepezil versus placebo on cognitive and motor performance in other neuropsychological tests

Conditions and MedDRA coding

neurological disorders

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Healthy volunteers
2. Male or female aged ≥ 50 years without upper age limit
3. Right-handed
4. BMI 18 - 32 kg/m2
5. Suitable for MRI
6. Written informed consent obtained according to international guidelines and local laws
7. Capacity to understand the nature, significance and consequences of the trial and the trial related procedures and to comply with them

Exclusion criteria 19

1. Known clinically significant cardiovascular, pulmonary, hepatic, renal, gastrointestinal, urological, immunologic, neurologic, oncologic or psychiatric disease or other condition that, in the opinion of the investigator, would jeopardize the safety of the subject or the validity of the study results
2. Known QTc prolongation and/or family history of QTc prolongation
3. Known electrolyte imbalance (hypokalemia, hypomagnesemia)
4. Known claustrophobia
5. Known defective vision of > +/- 6 dioptres if not corrected by contact lenses
6. Known hypersensitivity to the active substances, piperidine derivatives or any of the excipients of the IMP / Placebo according to the SmPc
7. Current use and/or use up to 30 days prior to study entry of: 1. Nicotine; 2. Substances that influence the QTc interval according to SmPC; 3. Non-steroidal anti-inflammatory drugs (NSAIDs) on a regular long-term basis; 4. Donepezil hydrochloride or related drugs with anti- and cholinergic activity and neuromuscular blocking agents according to SmPc; 5. CYP3A4 and 2D6 inhibitory and inducing substances according to SmPc: chinidin, itraconazole, erythromycin, fluoxetine, rifampicin, phenytoin, carbamazepine, systemic use of ketoconazole; 6. Beta blockers
8. After at least 3 minutes of rest in a sitting position, subjects should be excluded from the study if they have the following vital signs at screening: 1. systolic blood pressure outside the range of 90-145 mmHg, or 2. diastolic blood pressure outside the range of 50-90 mmHg, or 3. resting heart rate outside the range of 40-100 beats per minute
9. Abnormal ECG values during screening
10. Planned surgery within the study and follow-up period
11. Metal implants and/or components on the body that cannot be removed
12. Participation in any other interventional clinical trial within the last 30 days before the start of this trial and/or simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
13. Previous participation in this trial
14. Known abuse of medication, drugs or alcohol
15. Person who is in a relationship of dependence/employment with the Sponsor or the Principle Investigator
16. Person who lack of sufficient communication skills in the German language
17. Person who is institutionalised by court or official order
18. Current or planned pregnancy, nursing period
19. Failure to use one of the following safe methods of contraception: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Dual-task costs (DTC): calculated as the difference between the scores of the dual-task and single-task performances and measured as reaction time (ms) in the cognitive task and motor pedaling speed (ms) in the motor task after donepezil or placebo administration, respectively, at V1 and 2

Secondary endpoints 2

1. Neuronal activity: measured after donepezil or placebo administration, respectively, by fMRI during task performance at visit 1 and 2
2. Relative cognitive and motor performances in other neuropsychological tests: 1. measured by reaction times (ms) and % correct responses in the sub-tests of TAP-M test battery and 2. measured by time (s) conducting the TUG-test variant, both after donepezil or placebo administration, respectively, at V1 and 2

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Carl Von Ossietzky Universitaet Oldenburg

Sponsor organisation

Carl Von Ossietzky Universitaet Oldenburg

Address

Ammerlaender Heerstrasse 114-118, Wechloy Wechloy

City

Oldenburg

Postcode

26129

Country

Germany

Scientific contact point

Organisation

Carl Von Ossietzky Universitaet Oldenburg

Contact name

Coordinating Scientist

Public contact point

Organisation

Carl Von Ossietzky Universitaet Oldenburg

Contact name

Coordinating Scientist

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 13 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications