The Effect of Donepezil on Sedation and Other Symptoms

April 5, 2016 updated by: M.D. Anderson Cancer Center

Donepezil for Cancer Patients With Sedation Related to Opioid Treatment: A Double-blind Placebo Controlled Randomized Study

Primary Objective:

1. To determine the effectiveness of donepezil as compared to placebo for the management of opiate-induced sedation/drowsiness in patients with stable cancer pain

Secondary Objectives:

  1. To assess the side-effects in both groups of 1 week treatment of 5 mg donepezil and placebo
  2. To assess the effects of donepezil on fatigue (FACIT-Fatigue), and other symptoms (Anderson Symptom Assessment Scale)
  3. To assess the effects of donepezil on cognition (Symbol Digit Modalities Test)
  4. To assess the effects of donepezil on constipation (number of bowel movements)

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Donepezil is currently used in the treatment of certain types of mental disorders, including Alzheimer's disease. Recent research studies have shown that donepezil helps to improve drowsiness in cancer patients receiving opioid medication.

Before treatment starts, you will be asked to answer some questions regarding your cancer diagnosis, the medication you are taking, and the symptoms you are having (i.e. pain, fatigue, nausea, depression, anxiety, drowsiness, shortness of breath, appetite, sleep problem, constipation, and well-being) and a test for your cognitive status (matching specific numbers with given geometric figures) will be performed. It will take about 30 minutes to complete the evaluation. Women who are at risk of being pregnant must have a negative urine pregnancy test.

If you are qualified to enter the study you will be randomly assigned (as in the toss of a coin) to one of two groups. Participants in one group will receive donepezil for one week. Participants in the other group will receive a placebo (a tablet that does not contain any medication but looks just like the donepezil pill). You will have an equal chance (50/50) of being placed in either group. Neither you nor any the medical staff or researchers on this study will know if you are receiving the study drug or the placebo.

You will take 1 tablet of donepezil/placebo a day for 7 days. The research nurse will contact you by phone (in person if you are in the hospital) daily to ask questions about side effects and other symptoms.

On Day 8, you will need to come to the palliative care clinic for an evaluation. If you can not come to clinic on day 8, evaluation will be performed through telephone. Evaluation of sedation/drowsiness, pain, constipation, fatigue, side effects, effectiveness of the treatment, and a test of nervous system and cognitive status will be performed. If you develop intolerable side effects while on this study, the medication will be stopped and you will be removed from the study.

After evaluation on Day 8, all participants will be offered the chance to receive 1 tablet of donepezil every day for 7 days. The research nurse will follow up with you by phone (in person if you are in the hospital) 3 or 4 days after you received donepezil (open label) to ask questions about side effects and other symptoms.

On Day 15, you will need to come to the palliative care clinic for an evaluation. Evaluation of sedation/drowsiness, pain, constipation, fatigue, side effects, effectiveness of the treatment, and a test of nervous system and cognitive status will be performed. You will be given an option to continue on an additional 8 weeks. During these 8 weeks, the follow up will be conducted by your primary physician.

This is an investigational study. Donepezil has been approved by FDA and is a commercially available drug. Its use in this study is investigational. It can continue to be prescribed by your primary physician after that time if needed. A total of 100 patients will take part in this study. All will be enrolled at M. D. Anderson.

Study Type

Interventional

Enrollment (Actual)

27

Phase

  • Phase 3

Contacts and Locations

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

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • U.T. M.D. Anderson Cancer Center

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

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patient with drowsiness/sedation caused by opiate for > 3 days and its intensity more or equal to 3/10 (0 to 10 scale; 0 = no sedation, 10=worst possible sedation).
  2. Patient receiving a regular dose of a strong opioid for the treatment of cancer pain, and no dose changes or dose change within 50% for at least 48 hours.Regular administration, defined as short acting opioids oral or parenteral every 4 hours around clock, slow release oral opioids every 12 hs or 24 hs, or transdermal opioids every 72 hours. Strong opioids include morphine, hydromorphone, methadone, fentanyl, and oxycodone.
  3. Patient with relatively intact cognition defined by the Mini Mental State Examination according to age and educational level. A score of 24 or above is usually considered normal.
  4. Patient willing to engage in follow up visit with a nurse by phone on day 2-7 (each day), 11 and 15 of the study and to return for follow up visit on day 8 of treatment. If patient is unable to come to clinic, assessment will be performed through telephone.
  5. Sexually active females at risk of being pregnant with a negative urine pregnancy test
  6. Written consent form signed.
  7. Patients are 18 years or older
  8. Concurrent radiation treatment (defined as 10 or less fractions for a palliative indication) is allowed
  9. Concurrent chemotherapy is allowed, if the first two cycles have been well tolerated (defined as no grade 3 or 4 non-hematological toxicity)

Exclusion Criteria:

  1. Major contraindication to donepezil i.e. hypersensitivity to donepezil or piperidine derivatives.
  2. Patients in whom a major change in opiate dose, analgesia requirements, anesthetic procedures or general anesthetic is expected over the next seven days.
  3. Treatment with anti-cholinergic agents (i.e., glycopyrrolate)
  4. Patients taking Methylphenidate.
  5. Patients with tube feeding (due to difficulty of accurate assessing some of the symptoms such as appetite and anorexia).
  6. History of ongoing arrhythmia causing a rhythm other than a sinus rhythm

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Donepezil
Oral Donepezil 5 mg daily x 7 days
Drug: Donepezil
5 mg once a day by mouth for 7 day cycle. After evaluation on Day 8, all participants will be offered donepezil every day for 7 days.
Other Names:
  • Aricept
Placebo Comparator: daily x 7 days
Placebo tablet daily x 7 days
Drug: Placebo
Placebo tablet once a day by mouth for one 7 day cycle. After evaluation on day 8, all participants offered donepezil every day for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Sedation Mean Scores at 1-Week
Time Frame: Baseline and Day 7
Anderson Symptom Assessment Scale (ASAS) was used to measure sedation mean scores (SD) on a 0-10 scale with 0 representing "not drowsy" and 10 representing "worst possible drowsiness."
Baseline and Day 7

Collaborators and Investigators

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

Sponsor

M.D. Anderson Cancer Center

Collaborators

Pfizer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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

November 1, 2003

Primary Completion (Actual)

July 1, 2007

Study Completion (Actual)

July 1, 2007

Study Registration Dates

First Submitted

July 12, 2006

First Submitted That Met QC Criteria

July 12, 2006

First Posted (Estimate)

July 14, 2006

Study Record Updates

Last Update Posted (Estimate)

May 9, 2016

Last Update Submitted That Met QC Criteria

April 5, 2016

Last Verified

December 1, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2003-0425

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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