The CIRCADIAN Study: Evaluation of Modulating Effect of Galantamine on Circadian Rhythm in Patients With Mild to Moderate Alzheimer's Disease

• Sponsor: Janssen-Cilag, S.A. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01181921
• Collaborator: (none)
• Enrollment: 1
• Location: 1
• Arm: 1
• Duration (Months): 1
• Patients Per Site Per Month: 1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease	Drug: Galantamine	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• 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 Start Date: May 1, 2011
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Galantamine	Drug: Galantamine; Type= range, unit= mg, number= 8-24, form= capsule, route= oral use. The starting dose will be 8 mg/day for 4 weeks. Subsequently, the initial maintenance dose will be 16 mg/day for 4 weeks. Then, an increase to the maintenance dose of 24 mg/day should be considered on an individual basis after appropriate assessment.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Sleep/Wake Patterns as Measured by Actigraph at 12 Weeks [Baseline and 12 weeks]

   Actigraph is a small portable device that is worn on the wrist of the non-dominant arm to measure body movement during long time periods. It creates a pattern based on activity that is useful in assessing sleep-wake cycles across many consecutive days and nights. It is useful for assessing sleep phase disorders.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Barcelona		Spain

Sponsors and Collaborators

• Janssen-Cilag, S.A.

Investigators

• Study Director: Janssen-Cilag S.A. (formerly Janssen Sp) Clinical Trial, Janssen-Cilag, S.A.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Janssen-Cilag, S.A.
• ClinicalTrials.gov Identifier: NCT01181921
• Other Study ID Numbers: CR015586; GALALZ4041; 2009-013689-18
• First Posted: Aug 13, 2010
• Last Update Posted: May 1, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Janssen-Cilag, S.A.: Alzheimer Disease; Dementia; Sleep Disorders; Galantamine; Reminyl
• Additional relevant MeSH terms: Alzheimer Disease; Galantamine

Study Results

Participant Flow

Pre-assignment Detail	Only one participant was recruited and did not complete the study; therefore no assessments have been conducted throughout the study.

Arm/Group Title	Galantamine
Arm/Group Description	Galantamine (capsules/oral use). Starting dose: 8 mg/day for 4 weeks; initial maintenance dose: 16 mg/day for 4 weeks; then, an increase to the maintenance dose of 24 mg/day should be considered on an individual basis after appropriate assessment.
Period Title: Overall Study
STARTED	1
COMPLETED	0
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Galantamine
Arm/Group Description	Galantamine (capsules/oral use). Starting dose: 8 mg/day for 4 weeks; initial maintenance dose: 16 mg/day for 4 weeks; then, an increase to the maintenance dose of 24 mg/day should be considered on an individual basis after appropriate assessment.
Overall Participants	1
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	1 100%
Sex: Female, Male (Count of Participants)
Female	1 100%
Male	0 0%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Sleep/Wake Patterns as Measured by Actigraph at 12 Weeks
Description	Actigraph is a small portable device that is worn on the wrist of the non-dominant arm to measure body movement during long time periods. It creates a pattern based on activity that is useful in assessing sleep-wake cycles across many consecutive days and nights. It is useful for assessing sleep phase disorders.
Time Frame	Baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Only one participant was recruited and did not complete the study; therefore no assessments have been conducted throughout the study.

Arm/Group Title	Galantamine
Arm/Group Description	Galantamine (capsules/oral use). Starting dose: 8 mg/day for 4 weeks; initial maintenance dose: 16 mg/day for 4 weeks; then, an increase to the maintenance dose of 24 mg/day should be considered on an individual basis after appropriate assessment.
Measure Participants	0

Adverse Events

Time Frame	12 weeks
Arm/Group Title	Galantamine
Arm/Group Description	Galantamine (capsules/oral use). Starting dose: 8 mg/day for 4 weeks; initial maintenance dose: 16 mg/day for 4 weeks; then, an increase to the maintenance dose of 24 mg/day should be considered on an individual basis after appropriate assessment.
All Cause Mortality
	Galantamine
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Galantamine
	Affected / at Risk (%)	# Events
Total	0/1 (0%)
Other (Not Including Serious) Adverse Events
	Galantamine
	Affected / at Risk (%)	# Events
Total	0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Study results as well as all reports or publications related to the study, belong to the sponsor exclusively. If the investigator would like to public results in journals or scientific magazines, it has to be in agreement with the sponsor and according to the protocol.