fMRI-behavioral Study of Cholinergic Augmentation With Donepezil in Healthy Sleep Deprived Adults

NCT00800553 | Completed Phase 4 DMC

• 1 other identifier: CRT108999
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study was to characterize how the anti-cholinesterase inhibitor (AChE-I) donepezil modulates brain regions involved in visual short-term memory, episodic memory and inhibitory efficiency following 24 hours of total sleep deprivation using fMRI as an additional marker for drug effect.

Conditions

Sleep Deprivation

Keywords

sleep deprivation; fMRI; double blind crossover study

Outcome Measures

Primary Outcomes (2)

• fMRI signal change in response to cholinergic augmentation within the context of sleep deprivation

  approx 1 month

• behavioral changes (response accuracy in a visual short term memory task)

  approx 1 month

Study Arms (2)

donepezil

EXPERIMENTAL

donepezil, 5 mg p.o. for approx 2 weeks

Drug: donepezil

placebo

PLACEBO COMPARATOR

placebo

Drug: Placebo

Interventions

donepezil DRUG

5mg o.m. p.o. for approx. 2 weeks

Also known as: Aricept

donepezil

Placebo DRUG

5mg of placebo for approx. 2 weeks

placebo

Eligibility Criteria

• Age: 21 Years - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject is able to read and understand the Subject Information Sheet and comply with protocol requirements, instructions and protocol-stated restrictions.
• Prior to any screening procedures, the subject and the physician must have signed a study-specific Informed Consent Form. No study-related procedures may be performed before the physician has obtained written informed consent from the subject.
• The subject is between 21 years to 35 years of age.
• The subject has a BMI of between 18.5 kg/m2 to 32 kg/m2 and body weight ≥ 50 kg.
• The subject is right-handed.
• The subject has a resting pulse \>40 bpm and \<90 bpm (normal range). The subject has a resting systolic blood pressure of between 91 mmHg to 140 mmHg (supine normal range) and a resting diastolic blood pressure of between 51 mmHg to 90 mmHg (supine normal range).
• The subject, in the opinion of the investigator, is in good health on the basis of a pre-study physical examination, medical history, vital signs, electrocardiogram (ECG), and the results of blood chemistry, haematology, and serology tests, and a urinalysis. A subject with a clinical abnormality or laboratory parameters outside the reference range for this age group may be included only if the Investigator considers that the finding will not introduce additional risk factors and will not interfere with the study procedures.
• The subject has habitual good sleeping habits: sleeping on average 6.5 to 9 hours each night in the past month.
• Have regular sleeping hours whereby they sleep no later than 1 am and rise before 9 am each day.
• Have no history of excessive daytime sleepiness or insomnia.
• Score no greater than 22 on the Morningness-Eveningness scale \[Horne and Ostberg, 1976\].
• If female, the subject must use a double barrier method of contraception (2 separate methods of contraception) from Screening until final discharge from the study. Oral contraceptives are not allowed.

You may not qualify if:

• The subject has taken prohibited medication within 1 week (or 14 days if the drug is a potential enzyme inducer) or within 5 half-lives prior to first dosing for any medication ingested, whichever is longer) prior to first dosing, unless in the opinion of the investigator and sponsor, the medication will not interfere with the study procedures or compromise safety. Prohibited medication is any prescribed medication or over-the-counter (OTC) medication, including high-dose vitamins or dietary supplements, or any herbal medicine known to interfere with the metabolic CYP pathways, (e.g. St. John's Wort) or cognitive function (e.g. ginko). Paracetamol for mild analgesia will be permitted.
• The subject has a significant history of drug or alcohol abuse, defined as an alcohol intake greater than 21 units per week or a history of drug abuse within the last 6 months, or a history of substance abuse deemed significant by the investigator. A unit of alcohol is defined as 250 mL of lager/beer, 100 mL of Wine, or 25 mL of spirits.
• The subject has an orthostatic blood pressure reduction \>20 mmHg (based on the difference of systolic blood pressure between supine and after standing for 1 minute).
• The subject has been exposed to more than 3 new chemical entities (NCEs) within 12 months prior to the first dosing day, or participated in a trial with any drug within 84 days before the start of the study, or participated in a trial with a NCE within 112 days before the start of the study.
• History or presence of hypersensitivity to the study drugs or drugs of this class (hyoscine, atropine, donepezil) or a history of other severe drug allergy or hypersensitivity which, in the opinion of the physician responsible, contraindicates their participation.
• The subject has a serious illness, such as liver or renal insufficiency, or a cardiovascular, pulmonary, gastrointestinal, endocrine, neurological, infectious, neoplastic, or metabolic disturbance or other condition known to interfere with the absorption, distribution, metabolism or excretion of drugs.
• The subject has history or presence of peptic ulcer disease, cardiac arrhythmias, cardiac conduction abnormalities, asthma or obstructive pulmonary disease.
• The subject has history or presence of psychiatric or neurological illness, obstructive sleep apnea, narcolepsy or periodic leg movements as ascertained by questionnaire.
• If participation in the study will result in the subject having donated more than 1500 mL blood in the previous 12 months and where participation in study would result in donation of blood in excess of 500 mL within a 56 day period.
• The subject smokes more than 10 cigarettes per day or uses other nicotine containing products equivalent to 10 cigarettes per day (for example, snuff, nicotine patch, nicotine chewing gum, mock cigarettes, or inhalers) and is not able to refrain from using nicotine containing products during the complete study period.
• The subject tested positive after screening or at baseline for drugs of abuse (opiates, methadone, cocaine, amphetamines, barbiturates, benzodiazepines, and cannabinoids).
• Caffeine intake of greater than 5 drinks per day on average.
• Presence of glaucoma or raised intraocular pressure based on medical history.
• Has an abnormality on acoustic function.
• The presence of a cardiac pacemaker or other electronic device or ferromagnetic metal foreign bodies.

Sponsors & Collaborators

• Duke-NUS Graduate Medical School: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Cognitive Neuroscience Laboratory, Duke-NUS Graduate Medical School

Singapore, 169611, Singapore

Location

Related Publications (1)

• Chuah LY, Chee MW. Cholinergic augmentation modulates visual task performance in sleep-deprived young adults. J Neurosci. 2008 Oct 29;28(44):11369-77. doi: 10.1523/JNEUROSCI.4045-08.2008.

  PMID: 18971479 RESULT

Related Links

• Cognitive Neuroscience Lab Webpage

MeSH Terms

Conditions

Sleep Deprivation

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Study Officials

• Michael WL Chee, MBBS, MRCP

  Duke-NUS Graduate Medical School

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 1, 2008
• First Posted: December 2, 2008
• Study Start: November 1, 2006
• Primary Completion: May 1, 2007
• Study Completion: May 1, 2007
• Last Updated: August 3, 2016

Record last verified: 2016-08

Locations

SG (1)