Role of Methadone As Co-Opioid Analgesic
Condition: Pain
Intervention: Morphine; Methadone
Intervention description: Arm 1: 2 Doses of "Slow-Release" Morphine PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days)."Immediate-release" morphine may be used, if needed, for pain.; 1 Dose of Methadone PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days)
Arm 2: 1 Dose of Slow-Release Morphine PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days).)."Immediate-release" morphine may be used, if needed, for pain.
Intervention MeSH terms: Morphine; Methadone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 5.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Solid Tumors; Morphine; Methadone; Co-Opioid Analgesic; Pain

Summary:

      Objectives:

      Primary Objective:

      To determine whether the addition of low dose methadone to morphine(in the methadone group)
      has a lower dose escalation index as compared to the morphine alone(in the morphine group) at
      Day 15 (+/- 3 days)

      Secondary Objectives:

      To determine whether individuals on the methadone arm have lower pain intensity than the
      morphine alone arm as demonstrated by a decrease in two points from baseline (+/- 3 days) in
      their ESAS score at Day 15 (+/- 3 days).

      To determine whether the methadone group of experiences fewer opioid induced neurotoxic side
      effects (including sedation, myoclonus, hallucinations, hyperalgesia and confusion) as
      compared to the morphine alone group at Day 15 (+/- 3 days).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Individual reporting average pain score for the last 24 hours that is at least a 4 on
             a numerical scale from 0 to 10 (0= no pain, 10=the worst possible pain) with a history
             of cancer (active or no evidence of disease).

          2. Individual is receiving strong opioids (morphine, fentanyl, oxycodone, hydromorphone)
             for 3 weeks prior to enrollment.

          3. Individual requires at least 150 mg of daily morphine equivalent daily dose for cancer
             pain. Using the formula MEDD = dose X MEDD Factor (App L) it would be follows:
             morphine: a 24 hour total oral intake (sum of PRN and around the clock doses) of 150
             mg or greater would qualify the patient, for fentanyl alone: a 24 hour total
             transdermal intake of 75mcg/h or greater would qualify the patient, for oxycodone
             alone: a 24 hour total oral intake of 100 mg or greater would qualify the patient, and
             for hydromorphone alone: a 24 hour total oral intake of 30 mg/day or greater would
             qualify the patient.

          4. Individual has the ability to receive morphine or methadone orally.

          5. Individual has no known allergy of history of severe toxicity to morphine or
             methadone.

          6. Individual has normal cognition defined as normal state of arousal and absence of
             obvious clinical findings of confusion, memory or concentration deficit.

          7. Individual has adequate renal function (creatinine less or equal to 2.0 MG/DL)

          8. Individual has a Zubrod performance status of 3 or lower.

          9. Individual is willing to sign written informed consent.

         10. Individual is 18 years of age or older.

         11. Individual on stable doses(on same dose for at least one week) of nonopioid analgesics
             including NSAIDS, corticosteroids, gabapentin, pregabalin, or antidepressants
             prescribed for the purposes of pain control.

        Exclusion Criteria:

          1. Individual is determined incapable of completing the evaluation forms.

          2. Individual with clinically evident impaired cognition.

          3. Patient with MEDD greater than 600.