PainPhase 2NCT00558870
Role of Methadone As Co-Opioid Analgesic
A Phase 2 study testing Morphine and Methadone in people with Pain, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain
- What is being tested?
- Morphine and Methadone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to Jan 2015
- Phase
- Phase 2
- 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
- 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).
- Individual is receiving strong opioids (morphine, fentanyl, oxycodone, hydromorphone) for 3 weeks prior to enrollment.
- 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.
- Individual has the ability to receive morphine or methadone orally.
- Individual has no known allergy of history of severe toxicity to morphine or methadone.
- Individual has normal cognition defined as normal state of arousal and absence of obvious clinical findings of confusion, memory or concentration deficit.
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- Individual has adequate renal function (creatinine less or equal to 2.0 MG/DL)
- Individual has a Zubrod performance status of 3 or lower.
- Individual is willing to sign written informed consent.
- Individual is 18 years of age or older.
- 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.
Who cannot join
- Individual is determined incapable of completing the evaluation forms.
- Individual with clinically evident impaired cognition.
- Patient with MEDD greater than 600.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: Role of Methadone As Co-Opioid Analgesic in Cancer Patients
Objectives:
Primary Objective:
Read more
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).
Read the detailed description
The Study Drugs:
Methadone and morphine are both designed to block pain receptors (cells that are sensitive to particular drugs) in your nerves and brain.
Study Groups and Study Drug Administration:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in toss of a coin) to 1 of 2 groups. Participants in Group 1 will stay on morphine only. Participants in Group 2 will receive morphine plus methadone. You will have an equal chance (50/50) of being placed in either of the 2 groups. You, the medical staff, and study researchers will not know which group you have been assigned to. If necessary, your doctor will be able to find out what group you are in the event of an emergency.
Participants in Group 1 will take 2 doses of "slow-release" morphine by mouth every 12 hours, every day for 15 days (plus or minus 3 days). You will also have access to "immediate-release" morphine to be used, as needed, for pain. If you need more than 3 of these immediate-release doses in a 24-hour period, you should call your study doctor.
Participants in Group 2 will take 1 dose of slow-release morphine and 1 dose of methadone by mouth every 12 hours, every day for 15 days (plus or minus 3 days). You will also have access to immediate-release morphine to be used, as needed, for pain. If you need more than 3 of these immediate-release doses in a 24-hour period, you should call your study doctor.
You will complete a questionnaire once daily about symptoms and pain you may be experiencing. It will take about 5 minutes to complete each time.
You will be provided with a drug diary to write down when and how often you take pain medication.
Study Visits:
On Days 8 and 15 (plus or minus 3 days) the following test and procedures will be performed:
- You will complete 3 questionnaires about any side effects you may be having. They will take about 15-20 minutes to complete.
- You will have tests to see how sensitive your skin is.
On Day 15 only (plus or minus 3 days), you will have blood (about 1 teaspoon) drawn to measure kidney function.
Length of Study:
You will be off-study after Day 15 (plus or minus 3 days). You will be taken off study early if the disease gets worse or intolerable side effects occur.
This is an investigational study. Methadone and morphine are both FDA approved and commercially available. Their use together is investigational. Up to 60 patients will take part in this study. All will be enrolled at M. D. Anderson.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MorphineDrug
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.
MethadoneDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Morphine Only | Active comparator | Morphine - 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. Receives: Drug: Morphine |
| Morphine + Methadone | Active comparator | 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.
1 Dose of Methadone PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days) Receives: Drug: Morphine; Drug: Methadone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Objective Response (OR)
Objective response (OR) is defined as a dose escalation index <20 where Opioid escalation index measured in milligrams is calculated by the formula, (OMD-OSD)/days, OMD = Opioid maximum dose as expressed in equianalgesic dose of oral morphine in milligrams, OSD= Opioid starting dose at the time of referral to palliative care/ pain specialist for the treatment of cancer pain as expressed in equianalgesic dose of oral morphine in milligrams. A low index indicates the achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time. OR used in determining 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.
Measured: Day 15 (+/- 3 days)
Dose Escalation Index at Day 15 (+/- 3 Days)
Intended index period from baseline to Day 15 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). To determine whether the methadone group of individuals has a lower dose escalation index as compared to the morphine alone group: Participant dosages measured at baseline and daily until end of study (day 15), total daily dose of methadone converted to daily morphine equivalent daily dose for cancer pain and added to total daily morphine dosages. From these daily values, maximum dose recorded will be Opioid Maximum Dose (OMD). Opioid escalation index measured as described in Outcome 1 above (milligrams calculated by formula, (OMD-OSD)/days). Low index indicates achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time.
Measured: Day 15 (+/- 3 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2007 (estimated)
- Study startNov 2007
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: Low 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 PainStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sriram Yennurajalingam, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00558870
- Sponsor's protocol ID
- 2006-0641
- Other IDs
- NCI-2012-01553
- Status last verified
- Mar 2016
- First submitted
- 14 Nov 2007
- Last updated
- 5 Apr 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Methadone As Co-Opioid Analgesic in Cancer Patients
- ClinicalTrials.gov ID
- NCT00558870
- Acronym / sponsor ID
- 2006-0641
- Conditions
- Pain
- Keywords
- Solid Tumors, Morphine, Methadone, Co-Opioid Analgesic, Pain
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low Accrual.
- Enrolment
- 5 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- Nov 2007
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 15 Nov 2007 (estimated)
- Results
- Posted 5 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The Study Drugs:
Methadone and morphine are both designed to block pain receptors (cells that are sensitive to particular drugs) in your nerves and brain.
Study Groups and Study Drug Administration:
If you are found to be eligible to take part in this study, you will be randomly assigned (as in toss of a coin) to 1 of 2 groups. Participants in Group 1 will stay on morphine only. Participants in Group 2 will receive morphine plus methadone. You will have an equal chance (50/50) of being placed in either of the 2 groups. You, the medical staff, and study researchers will not know which group you have been assigned to. If necessary, your doctor will be able to find out what group you are in the event of an emergency.
Participants in Group 1 will take 2 doses of "slow-release" morphine by mouth every 12 hours, every day for 15 days (plus or minus 3 days). You will also have access to "immediate-release" morphine to be used, as needed, for pain. If you need more than 3 of these immediate-release doses in a 24-hour period, you should call your study doctor.
Participants in Group 2 will take 1 dose of slow-release morphine and 1 dose of methadone by mouth every 12 hours, every day for 15 days (plus or minus 3 days). You will also have access to immediate-release morphine to be used, as needed, for pain. If you need more than 3 of these immediate-release doses in a 24-hour period, you should call your study doctor.
You will complete a questionnaire once daily about symptoms and pain you may be experiencing. It will take about 5 minutes to complete each time.
You will be provided with a drug diary to write down when and how often you take pain medication.
Study Visits:
On Days 8 and 15 (plus or minus 3 days) the following test and procedures will be performed:
- You will complete 3 questionnaires about any side effects you may be having. They will take about 15-20 minutes to complete.
- You will have tests to see how sensitive your skin is.
On Day 15 only (plus or minus 3 days), you will have blood (about 1 teaspoon) drawn to measure kidney function.
Length of Study:
You will be off-study after Day 15 (plus or minus 3 days). You will be taken off study early if the disease gets worse or intolerable side effects occur.
This is an investigational study. Methadone and morphine are both FDA approved and commercially available. Their use together is investigational. Up to 60 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, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Morphine Only | Active comparator | Drug: MorphineMorphine - 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. |
| Morphine + Methadone | Active comparator | Drug: Morphine, Drug: MethadoneArm 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. 1 Dose of Methadone PO Every 12 Hours, Every Day for 15 Days (plus or minus 3 days) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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).
- Individual is receiving strong opioids (morphine, fentanyl, oxycodone, hydromorphone) for 3 weeks prior to enrollment.
- 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.
- Individual has the ability to receive morphine or methadone orally.
- Individual has no known allergy of history of severe toxicity to morphine or methadone.
Key exclusion criteria (3 listed)
- Individual is determined incapable of completing the evaluation forms.
- Individual with clinically evident impaired cognition.
- Patient with MEDD greater than 600.
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 |
|---|---|---|
| MorphineArm 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. | Drug | Morphine + Methadone, Morphine Only |
| Methadone1 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. | Drug | Morphine + Methadone |
Primary outcome
Number of Participants With Objective Response (OR)
Time frame: Day 15 (+/- 3 days)
Objective response (OR) is defined as a dose escalation index <20 where Opioid escalation index measured in milligrams is calculated by the formula, (OMD-OSD)/days, OMD = Opioid maximum dose as expressed in equianalgesic dose of oral morphine in milligrams, OSD= Opioid starting dose at the time of referral to palliative care/ pain specialist for the treatment of cancer pain as expressed in equianalgesic dose of oral morphine in milligrams. A low index indicates the achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time. OR used in determining 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.
Dose Escalation Index at Day 15 (+/- 3 Days)
Time frame: Day 15 (+/- 3 days)
Intended index period from baseline to Day 15 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). To determine whether the methadone group of individuals has a lower dose escalation index as compared to the morphine alone group: Participant dosages measured at baseline and daily until end of study (day 15), total daily dose of methadone converted to daily morphine equivalent daily dose for cancer pain and added to total daily morphine dosages. From these daily values, maximum dose recorded will be Opioid Maximum Dose (OMD). Opioid escalation index measured as described in Outcome 1 above (milligrams calculated by formula, (OMD-OSD)/days). Low index indicates achievement of adequate analgesia or appearance of uncontrollable side effects limiting upward titration over time.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- University of Texas 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.
Sriram Yennurajalingam, 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 2 study testing Morphine and Methadone in people with Pain, 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 11 inclusion and 3 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 5 Apr 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 5 Apr 2016). 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?
Number of Participants With Objective Response (OR) (time frame: Day 15 (+/- 3 days)). The study lists 2 primary outcomes in all. 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 5 Apr 2016.