Clinical trial NCT01181921: The CIRCADIAN Study: Evaluation of Modulating Effect of Galantamine on Circadian Rhythm in Patients With Mild to Moderate Alzheimer's Disease
Official title: Phase IV Study for the Assessment of Modulating Effect of Galantamine (Reminyl PRC) on Circadian Rhythm in Patients With Moderate Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Alzheimer Disease
Keywords: Alzheimer Disease
Dementia
Sleep Disorders
Galantamine
Reminyl
Lead sponsor: Janssen-Cilag, S.A.
Sponsor class: INDUSTRY
First posted: 2010-08-13
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to assess the modulating effect of galantamine on circadian rhythm in patients with moderate Alzheimer's disease.

Detailed description: This is a pilot, single-group, interventional, prospective study including patients with moderate Alzheimer's disease, treated with galantamine. Galantamine is thought to benefit the cognitive functioning of those with Alzheimer's disease. The starting treatment dose is 8 mg/day for 4 weeks. The initial maintenance dose of galantamine is 16 mg/day. Patients should be maintained on 16 mg/day for 4 weeks. An increase to the maintenance dose of 24 mg/day should be considered on an individual basis after the appropriate assessment including evaluation of clinical benefit and tolerability. For individual patients not showing an increased response or not tolerating 24 mg/day, a dose reduction to 16 mg/day should be considered. The primary objective is the assessment of the modulating effect of galantamine (Reminyl PRC) on circadian rhythm (wake/sleep) in patients with moderate Alzheimer's disease. The secondary objective is to assess the perception of the physicians, caregivers and patients themselves on sleep-wake disorders in patients with moderate Alzheimer's disease before and after treatment with galantamine. Sleep disturbances will be assessed by two actigraphy measures: one, before starting treatment, and the other, 12 weeks after the first actigraphic measure. The primary endpoint is the day/night ratio measured by the actigraphy before and after treatment with galantamine in patients with moderate Alzheimer-type dementia. Concerning the Efficacy Measures, the Actigraphy will be used as a method to assess the modulating effect of galantamine on circadian rate. The impact of this modulating effect on the caregivers, patients themselves and physicians will be assessed by three questionnaires: the Zarit Caregiver Burden Interview (ZBI), the Pittsburgh Sleep Quality Index (PSQI) and the Clinical Global Impression (CGI), respectively. Patient safety will be monitored. It is estimated that the study period will range from September 2010 to the second quarter of 2011.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Alzheimer-type dementia according to the definition of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM IV-TR) and a diagnosis of possible or probable Alzheimer-type dementia, according to NINCDS-ADRDA classification (American Psychiatric Association, 2000
* McKhann, G. et al, 1984)
* should have moderate dementia, evidenced by a Mini-Mental Status examination (MMSE) score between 12 and 20, including these limits
* At inclusion, a recent CT or MRI must be available
* Physical examination and the electrocardiogram (ECG) performed at the screening visit must be normal or consistent with the underlying illness in the study population
* History of sleep behavior changes (eg: insomnia, daytime sleepiness, changes in sleep/wakefulness cycle) 2 or more weeks before, reported by the caregiver
* Patients should have a caregiver sufficiently informed of their condition and, if possible, living with them
* Patients (or their legally-acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion Criteria:

* History of other neurodegenerative disorders, such as Parkinson's disease, Pick disease or Huntington's chorea, Down syndrome, Creutzfeldt-Jakob disease (patients with mild extrapyramidal signs for which no treatment is required are not excluded from the trial)
* Clinically significant cardiovascular disease expected to limit the ability of the patient to participate and complete the study
* Any history of epilepsy or seizures (except for febrile seizures in childhood)
* Clinically significant psychiatric condition, according to the DSM-IV criteria, particularly major depression or schizophrenia currently
* Active peptic ulcer (treatment of the disease started \< 3 months or treatment is not successful
* Clinically significant liver, renal, pulmonary, metabolic, or endocrine disorders
* Clinically significant urinary flow obstruction
* History of or suspected alcoholism or drug abuse in accordance to the DSM-IV criteria, in the past year, or previous history of prolonged abuse
* Previous therapy with memantine or an acetylcholinesterase inhibitor (including galantamine)
* Patients receiving antipsychotics, hypnotic or sedative agents (those patients who need this kind of medication during the study would be withdrawn from the study and replaced)
* Bedridden patients

Primary outcomes:
measure: Change From Baseline in Sleep/Wake Patterns as Measured by Actigraph at 12 Weeks
timeFrame: Baseline and 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Barcelona
country: Spain
Study officials:
affiliation: Janssen-Cilag, S.A.
name: Janssen-Cilag S.A. (formerly Janssen Sp) Clinical Trial
role: STUDY_DIRECTOR
References: