Advanced CancerPhase 3NCT00352664
The Effect of Donepezil on Sedation and Other Symptoms
A Phase 3 study testing Donepezil in people with Advanced Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Cancer
- What is being tested?
- Donepezil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2003to Jul 2007
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
U.T. M.D. Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Donepezil for Cancer Patients With Sedation Related to Opioid Treatment: A Double-blind Placebo Controlled Randomized Study
Primary Objective:
- 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)
Read the 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.
- Conditions
- Advanced Cancer
- Being tested
- Donepezil, Placebo
- Keywords
- Advanced Cancer, Cancer Pain, Donepezil, Sedation, Placebo
- Medical subject headings
- Cancer Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DonepezilDrug
Also called Aricept
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Donepezil | Active comparator | Oral Donepezil 5 mg daily x 7 days Receives: Drug: Donepezil |
| daily x 7 days | Placebo comparator | Placebo tablet daily x 7 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sedation Mean Scores at 1-Week
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."
Measured: Baseline and Day 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2006 (estimated)
- Study startNov 2003
- Primary completionJul 2007
- Study completionJul 2007
Why it stopped: Low patient accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Advanced CancerStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Investigators
- Eduardo Bruera, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00352664
- Sponsor's protocol ID
- 2003-0425
- Status last verified
- Dec 2009
- First submitted
- 12 Jul 2006
- Last updated
- 9 May 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Donepezil for Cancer Patients With Sedation Related to Opioid Treatment: A Double-blind Placebo Controlled Randomized Study
- ClinicalTrials.gov ID
- NCT00352664
- Acronym / sponsor ID
- 2003-0425
- Conditions
- Advanced Cancer
- Keywords
- Advanced Cancer, Cancer Pain, Donepezil, Sedation, Placebo
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low patient accrual
- Enrolment
- 27 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Nov 2003
- Primary completion
- Jul 2007 (actual)
- Study completion
- Jul 2007 (actual)
- First posted
- 14 Jul 2006 (estimated)
- Results
- Posted 29 Dec 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Primary Objective:
- 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)
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil | Active comparator | Drug: DonepezilOral Donepezil 5 mg daily x 7 days |
| daily x 7 days | Placebo comparator | Drug: PlaceboPlacebo tablet daily x 7 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DonepezilAlso: Aricept5 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. | Drug | Donepezil |
| PlaceboPlacebo 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. | Drug | daily x 7 days |
Primary outcome
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."
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- UT MD Anderson Cancer Center websiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eduardo Bruera, MD principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Donepezil in people with Advanced Cancer, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 9 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sedation Mean Scores at 1-Week (time frame: Baseline and Day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 May 2016.