Safety and Efficacy of Divalproex and Quetiapine in Elderly Alzheimer's Dementia Patients

NCT ID: NCT00375557

Last Updated: 2015-05-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-10-31
• Study Completion Date: 2007-09-30

Brief Summary

The primary aim is to determine whether Divalproex ER or one of the atypical antipsychotics is more effective improving dementia related behavioral symptoms in patients with dementia, and evaluate the impact of such improvements on other clinical domains, such as quality of life, functional status.

Detailed Description

This clinical trial will be open label, flexible dose study of Divalproex ER vs Quetiapine for 6 weeks. Patients will be randomized to Divalproex ER vs Quetiapine outpatient / inpatient. The schedule of visits will include a screening, a baseline and 3 treatment visits / assessment. The End of Study/Early Termination visit will conclude the Trial. The safety follow-up visit will be scheduled only for the patients with unresolved Adverse Events detected prior or at the End of Study/Early Termination visit.

Conditions

Alzheimer's Disease; Dementia; Behavioral Symptoms

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Quetiapine

Group Type: ACTIVE_COMPARATOR

Quetiapine

Intervention Type: DRUG

Quetiapine will be initiated in 25 mg/day, with a variable dosing frequency (QD-TID). The daily dose of Quetiapine will be titrated up by 25-50 mg each day based on patients' response and tolerability, not to exceed a maximum of 750 mg/day.

2

Divalproex ER

Group Type: ACTIVE_COMPARATOR

Divalproex ER

Intervention Type: DRUG

Divalproex ER will be initiated on 250 mg/day, dosed once daily. The daily dose of Divalproex ER will be titrated up 250 mg each day based on patients' response and tolerability, not to exceed a maximum of 2000 mg/day.

Interventions

Divalproex ER

Divalproex ER will be initiated on 250 mg/day, dosed once daily. The daily dose of Divalproex ER will be titrated up 250 mg each day based on patients' response and tolerability, not to exceed a maximum of 2000 mg/day.

Intervention Type: DRUG

Quetiapine

Quetiapine will be initiated in 25 mg/day, with a variable dosing frequency (QD-TID). The daily dose of Quetiapine will be titrated up by 25-50 mg each day based on patients' response and tolerability, not to exceed a maximum of 750 mg/day.

Intervention Type: DRUG

Other Intervention Names

Depakote ER; Seroquel

Eligibility Criteria

Inclusion Criteria

1. Patients, men and women =/> 55 years of age.

2. Inpatient / Outpatients with diagnosis of Moderate to Severe probable Alzheimer's dementia as determined by the Structured Clinical Interview for DSM-IV.

3. Patients with a Mini Mental Status Examination scores between 3-15 at screening.

4. Patients and Care Giver/ Legal representative or Guardian who are able to comprehend and satisfactorily comply with protocol requirements.

5. Patient, Care Giver/ Legal representative or Guardian who signed the written informed consent given prior to entering any study procedure.

6. Patients who have been at least three month ongoing stable dose of cholinesterase enzyme inhibitors or memantine.

Exclusion Criteria

1. Patients with a concurrent DSM-IV Axis I diagnosis in any of the following categories:

1.1. Delirium, Amnestic and other Cognitive disorders 1.2. Lifetime Schizophrenia and other Psychotic Disorders 1.3. Lifetime Bipolar I Disorder 1.4. Bipolar 11 Disorder with an episode of hypomania within the last year 1.5. Alcohol or Substance Dependence or Abuse (excluding nicotine) in one month prior to the Screening Visit

2. Patients with a history of intolerance or hypersensitivity to Divalproex ER & Quetiapine.

3. Patients who have a history of seizures.

4. Patients who based on history or mental status examination have a significant risk of committing suicide.

5. Patients who are homicidal or violent and who are in the Investigator's opinion in significant imminent risk of hurting others.

6. Patients who have been treated with depot-neuroleptic within 3 months prior to the Baseline Visit.

7. Patients with a positive urine drug screen, unless proven to be prescribed for a short-term course of treatment. In these situations a urine drug screen must be repeated at least 7 days after the last dose of the prescription medication containing narcotics.

8. Patients who have participated in any clinical trial within one month prior to the Screening Visit, or in a clinical trial involving a psychotropic medication within the 3 months prior to the Screening Visit.

9. Patients who have a medical condition that, in the Investigator's opinion, would expose them to an increased risk of a significant adverse event or interfere with assessments of safety and efficacy during the course of the trial.

10. Patients with any current malignancy, or any clinically significant hematological, endocrine, cardiovascular, renal, hepatic, gastrointestinal or neurological disease (including any form of epilepsy). If there is a history of such disease but the condition has been stable for at least the past year and is judged by the investigator not to interfere with the patient's participation in the study, the patient may be included.

11. Patients with systolic blood pressure greater than 180 mm Hg or less than 90 mm Hg or diastolic blood pressure greater than 105 mm Hg or less than 50 mm Hg at the Screening visit.

12. Patients who test positive for Hepatitis B surface antigen or Hepatitis C antibody.

13. Patients whose laboratory values at the Screening visit will be 1.5 times greater than ULN.

14. Patients requiring concomitant treatment with any psychotropic drug (except zolpidem for sleep no more than 3x/week prn).

15. Patients who require concomitant therapy with any prohibited prescription.

16. Patients who are unable to speak, read, and understand English or are judged by the investigator to be unable or unlikely to follow the study protocol and complete all scheduled visits.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Abbott

INDUSTRY

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Muhammad Aslamm

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Muhammad Aslam, MD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati/ VA Medical Center

Locations

Cincinnati VA Hospital

Cincinnati, Ohio, United States

Countries

United States

References

Profenno LA, Jakimovich L, Holt CJ, Porsteinsson A, Tariot PN. A randomized, double-blind, placebo-controlled pilot trial of safety and tolerability of two doses of divalproex sodium in outpatients with probable Alzheimer's disease. Curr Alzheimer Res. 2005 Dec;2(5):553-8. doi: 10.2174/156720505774932205.

Reference Type: BACKGROUND

PMID: 16375658 (View on PubMed)

Other Identifiers

06-08-25-06

Identifier Type: -

Identifier Source: org_study_id