The Effect of Donepezil on Sedation and Other Symptoms - Full Text View

Sponsors and Collaborators:	M.D. Anderson Cancer Center Pfizer
Information provided by:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00352664

Purpose

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:

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

Condition	Intervention	Phase
Advanced Cancer	Drug: Donepezil Drug: Placebo	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Donepezil for Cancer Patients With Sedation Related to Opioid Treatment: A Double-Blind Placebo Controlled Randomized Study

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: E 2020 Donepezil

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Estimated Enrollment:	100
Study Start Date:	November 2003

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 of free drug. 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. The drug will be provided free of charge during and for up to 8 weeks after the study. 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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).
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.
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.
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.
Sexually active females at risk of being pregnant with a negative urine pregnancy test
Written consent form signed.
Patients are 18 years or older
Concurrent radiation treatment (defined as 10 or less fractions for a palliative indication) is allowed
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:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00352664

Locations

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

Sponsors and Collaborators

M.D. Anderson Cancer Center

Pfizer

Investigators

Principal Investigator:

Eduardo Bruera, MD

M.D. Anderson Cancer Center

More Information

No publications provided

Study ID Numbers:	2003-0425
Study First Received:	July 12, 2006
Last Updated:	July 30, 2007
ClinicalTrials.gov Identifier:	NCT00352664 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Advanced Cancer
Cancer Pain
Donepezil
Sedation
Placebo

Study placed in the following topic categories:

Nootropic Agents
Cholinesterase Inhibitors
Neurotransmitter Agents

Donepezil
Pain
Cholinergic Agents

Additional relevant MeSH terms:

Nootropic Agents
Cholinesterase Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses
Physiological Effects of Drugs

Donepezil
Enzyme Inhibitors
Cholinergic Agents
Central Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 03, 2009