The Effect of Donepezil on Sedation and Other Symptoms
Condition: Advanced Cancer
Intervention: Donepezil; Placebo
Intervention description: 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.; 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.
Intervention MeSH terms: Donepezil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Advanced Cancer; Cancer Pain; Donepezil; Sedation; Placebo

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. 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)
    

Eligibility criteria:

        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