The Effect of Donepezil in Radiotherapy-related Cognitive Impairment.

November 21, 2019 updated by: Yamei Tang, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

The Effect of Donepezil in Radiotherapy-related Cognitive Impairment: a Randomized, Double-blind, Placebo-controlled Clinical Trial

Purpose: This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the therapeutic effects of donepezil in radiotherapy-related cognitive impairment.

Further study details as provided by Sun Yat-sen Memorial Hospital, Sun Yat-sen University / Yameitang.

Primary outcome measure: cognitive improvement, which is determined by the difference value of ADAS-cog score before and after the treatment of donepezil.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Application of radiotherapy to patients with head and neck cancer is a mainstay treatment in contemporary oncology practice. However, patients who received radiation are vulnerable to development of cognitive impairment. There is no acknowledged and effective standard treatment for radiotherapy-related cognitive impairment. The investigators supposed that donepezil, as a cholinesterase inhibitor, would relieve radiotherapy-related cognitive impairment after head and neck cancer, and would improve the life quality for these patients and their families.

Primary objectives: This randomized, double-blind, placebo-controlled clinical trial aims to evaluate the efficacy of donepezil on cognition in radiotherapy-related cognitive impairment.

Secondary objectives:

To evaluate the effect of donepezil on sleep disorder, mood disorder, activities of daily living, and safety in patients with radiotherapy-related cognitive impairment.

OUTLINE: This is randomized, double-blind, placebo-controlled clinical trial. Patients will be enrolled and administrated with donepezil or placebo. Donepezil will be supplied as 10 mg per pill to be taken by mouth. Placebo will be supplied as substitute of 10 mg donepezil per pill to be taken by mouth.

Patients will be screened, consented, enrolled and have a washout period for 6 weeks. Then these patients will be randomized to two arms.

Arm І: Patients receive donepezil with a dosage of 5 milligram at 8 am for one week (Week 1), then 10 milligram at 8 am for 23 weeks (Week 2-24), in the absence of unacceptable toxicity or severe deterioration.

Arm ІI: Patients receive placebo with a dosage of one half pill at 8 am for one week (Week 1), then one pill at 8 am for 23 weeks (Week 2-24), in the absence of unacceptable toxicity or severe deterioration.

Study Type

Interventional

Enrollment (Anticipated)

238

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510120
        • Recruiting
        • Sun yat-sen memorial hospital
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

35 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • (1) Received radiation therapy due to head and neck cancer.
  • (2) Prior irradiation ≥ 1.5 years and ≤ 6 years.
  • (3) Age>/= 35 years and age</=60.
  • (4) Estimated life expectancy ≥ 12 months.
  • (5) Cognitive impairment ≥ 4 weeks, with MMSE total score ≤26, or MoCA total score ≤ 25.
  • (6) Routine laboratory studies: normal bilirubin, normal aspartate aminotransferase (AST or SGOT), normal alanine aminotransferase (ALT), normal creatinine, normal white-cell count; normal neutrophils count, normal platelets count; Hb >/=110 gram per millilitres; PT, APTT, INR in a normal range.
  • (7) Constant caregivers who well understand and have willingness to sign a written informed consent document.

Exclusion Criteria:

  • (1) evidence of tumor metastasis, recurrence, or invasion;
  • (2) evidence of very high intracranial pressure that suggests brain hernia and need surgery;
  • (3) previous treatment with donepezil or other medications for cognitive impairment;
  • (4) history of mental disorders, epilepsy, cognitive impairment before radiotherapy;
  • (5) history of stroke, or high risk of vascular dementia;
  • (6) family history of Alzheimer's disease, Pick's disease, etc.;
  • (7) history of severe head trauma;
  • (8) clinically significant active disease, e.g. New York Heart Association Grade II or greater congestive heart failure, serious and inadequately controlled cardiac arrhythmia, bradycardia, significant vascular disease, severe infection;
  • (9) history of allergy to relevant drugs;
  • (10) pregnancy, lactation, or fertility program in the following 12 months;
  • (11) participation in other experimental studies.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Donepezil
Patients receive donepezil with a dosage of 5 milligram at 8 am for one week (Week 1), then 10 milligram at 8 am for 23 weeks (Week 2-24), in the absence of unacceptable toxicity or severe deterioration.
Drug: Donepezil Hydrochloride
Donepezil will be used with a dosage of 5 milligram at 8 am for one week (Week 1), then 10 milligram at 8 am for 23 weeks (Week 2-24).
Placebo Comparator: Control
Patients receive placebo with a dosage of one half pill at 8 am for one week (Week 1), then one pill at 8 am for 23 weeks (Week 2-24), in the absence of unacceptable toxicity or severe deterioration.
Other: Placebo
Placebo will be used with a dosage of one half pill at 8 am for one week (Week 1), then one pill at 8 am for 23 weeks (Week 2-24).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
cognitive change
Time Frame: Baseline to Week 24
Cognitive change, which is determined by the difference value of ADAS-cog (Alzheimer's Disease Assessment Scale-cognitive subscale) before and after the treatment of donepezil. The rating of ADAS-cog is made on 6-point scale rating from 0 to 5 in 12 domains.
Baseline to Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
global condition change
Time Frame: Baseline to Week 24
Efficacy of donepezil on global condition using CIBIC-plus (Clinician's Interview-Based Impression of Change plus). The rating is made on a 7-point scale ranging from "1 = marked improvement" to "7 = marked worsening". A score of "4" indicates no change.
Baseline to Week 24
changes of activities of daily living
Time Frame: Baseline to Week 24
Efficacy of donepezil on activities of daily living using ADL (Activities of Daily Living). Total score is from 0 to 54. The higher score, the lower impairment.
Baseline to Week 24
cognition change
Time Frame: Baseline to Week 24
Efficacy of donepezil on mental statement using MMSE (Mini Mental Status Examination). The total score of MMSE is 30.
Baseline to Week 24
psychological statement change
Time Frame: Baseline to Week 24
Efficacy of donepezil on psychological statement, including sleep disorder, mood disorder etc. using Neuropsychiatric Inventory (NPI) total score.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Investigators

  • Principal Investigator: Yamei Tang, M.D., Sun Yat-sen Memorial Hospital,Sun Yat-sen University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 1, 2019

Primary Completion (Anticipated)

December 31, 2022

Study Completion (Anticipated)

December 31, 2022

Study Registration Dates

First Submitted

March 27, 2019

First Submitted That Met QC Criteria

April 6, 2019

First Posted (Actual)

April 9, 2019

Study Record Updates

Last Update Posted (Actual)

November 25, 2019

Last Update Submitted That Met QC Criteria

November 21, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2019002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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