Back to resultsDosing Intervals of Opioid Medication for Chronic Pain
Primary Purpose
Chronic Pain
Status
Withdrawn
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Extended Release Opioid Formulation, Shortened Intervals
Extended Release Opioid Formulation, Standard intervals
Placebo oral tablet
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Pain focused on measuring opioid
Eligibility Criteria
Inclusion Criteria:
- >18 years old
- willing and capable to give written informed consent
- diagnosis of chronic pain (> 3 months)
- current prescription for oxycodone controlled release or hydromorphone controlled release or morphine sustained release for pain
- Using extended release opioids at intervals less than 12 hours/ more than twice daily
Exclusion Criteria:
- ongoing acute pain episode
- use of immediate release opioids that contribute to more than 20% of their total daily opioid dose
- total daily morphine equivalent dose >400mg
- actively tapering their opioid dose
- use of multiple extended release opioid products
- unstable psychological diagnosis (using the Psychosocial Screening Interview Guide)
- outstanding or planned litigation related to pain
- pregnancy or lactation in women
- history of coronary artery disease
- active tapering or titration of benzodiazepines or cannabinoids
- positive urine drug screen for amphetamines, barbiturates, cocaine, methamphetamine, methadone, phencyclidine, propoxyphene or unexpected opioids or benzodiazepines
- using M-Eslon
- using long acting hydromorphone
- using Kadian
Sites / Locations
- University Health Network
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Shortened interval extended release opioid
Standard interval extended release opioid
Arm Description
Extended release opioid, individualized total daily dose, dosing intervals less than every 12 hours.
Extended release opioid, individualized total daily dose, dosing intervals every 12 hours
Outcomes
Primary Outcome Measures
Percentage of participants who complete both treatment periods and have evaluable Patient Global Impression and pharmacokinetic data
Feasibility outcome
Secondary Outcome Measures
Patient Global Impression of Change
Single-item rating by subjects of their improvement with treatment on a 7-point scale that ranges from the lowest rating of 1= 'very much improved' to the highest rating of 7= 'very much worse'. Higher values are considered to be a better outcome.
Numerical Pain Rating Scale
A measure of pain intensity. Ten point scale with a minimum of "0"= no pain to a maximum of "10" = worst pain imaginable. Higher scores represent a worse outcome.
Brief Pain Inventory (Short Form)
An inventory of questions about pain, including a pain diagram, pain intensity rating subscales and pain interference rating subscales. The four pain intensity rating subscales are "pain at worst", "pain at least", "pain on average" and "pain right now". These are 10-point scales with a minimum of "0" =no pain, and a maximum of "10"= pain as bad as you can imagine", where higher scores are worse. Pain intensity subscales can be combined as an average on the same scale of 0-10. The eight pain interference subscales measuring interference on general activity, mood, walking ability, work, relations with other people, sleep, enjoyment of life, are 10-point subscales which range a minimum of "0" = pain does not interfere, to a maximum of "10"=pain completely interferes with the item. Higher scores are worse outcomes. Pain interference subscales may be combined as an total score out of 80, or divided by eight to get an average of pain interference on the scale of 0-10.
Subjective Opioid Withdrawal Scale
A self-administered scale for grading 16 opioid withdrawal symptoms on a scale of '0' meaning 'not at all' to '4' meaning 'extremely'. Higher numbers are worse outcomes.
Addiction Research Centre Inventory (ARCI) - short form
The short version of the ARCI is a well-validated, standardized, self-report questionnaire of 49 "true-false" items and is used to differentiate subjective effects of drugs. True = 1, False = 0, responses to selected items are added for scores on different scales. Three of the scales are pertinent to opioid abuse liability: MBG (morphine-benzedrine group), a measure of euphoria, minimum = 0, and a maximum = 16); PCAG (pentobarbital-chlorpromazine-alcohol group) a measure of sedation, minimum =0, maximum=15; LSD (lysergic acid diethylamide scale) a measure of dysphoric and psychotomimetic changes, minimum=0, maximum =14. Higher scores are worse outcomes.
Profile of Mood States
A widely used, self-reported questionnaire for assessing drug-induced changes in mood. It has 72 adjectives and phrases describing feelings people have, and ask for the user to describe "how you are feeling right now" on a 5 point scale of descriptives: with a minimum value = 0 "Not at all", to a maximum value of 4= "extremely". Total mood disturbance is calculated by adding the results of the 6 subscales, and then subtracting the vigor -activity subscale (range 0-200). Subscales (six) are calculating by adding specific items: tension-anxiety (9 items, range 0-36), depression (15 items, range 0-60), anger-hostility (12 items, range 0-48), vigor-activity (8 items, range 0-32), fatigue (7 items, range 0-28), confusion-bewilderment (7 items, range 0-28).
Visual analogue scale - liking/high
Visual analog scales are 100mm lines, anchored at the ends by opposing adjectives (e.g. like-dislike). "Like" is at the minimum, 0mm mark, "dislike" is at the maximum, 100mm mark. Subjects are instructed to rate how they feel along a continuum by making a mark along the line. The measurement of drug liking is considered to be one of the most sensitive and reliable assessments of the likelihood of abuse of a drug. "Liking" and "High" at the 100mm marks would be considered worse outcomes in terms of likelihood of abuse of a substance.
Serum opioid concentrations
Serum opioid concentrations at 0,30 mins, 1,2,3,4,5,6 hours post-dose
Peak plasma concentration (Cmax)
The maximum concentration achieved post dose
Time to peak plasma concentration (Tmax)
Time that peak plasma concentration occurs post-dose
Area under the plasma concentration versus time curve (AUC)
Calculated area under the plasma concentration versus time curve, which describes exposure to the drug.
Abuse liability quotient (AQ)
The peak plasma concentration (Cmax) divided by the time to peak plasma concentration, which describes a calculation of the average rate of increase in plasma concentration over the interval between treatment administration and the time of peak plasma concentration.
Full Information
NCT ID
NCT04132011
First Posted
October 2, 2019
Last Updated
March 25, 2020
Sponsor
University Health Network, Toronto
Collaborators
Canadian Society of Hospital Pharmacists
1. Study Identification
Unique Protocol Identification Number
NCT04132011
Brief Title
Dosing Intervals of Opioid Medication for Chronic Pain
Official Title
Examining the Relationship Amongst Opioid Subjective Effects and Pharmacokinetics of Extended Release Opioids at Shortened Dosing Intervals in Patients With Chronic Pain: a Randomized, Blinded, N-of-1 Case Series Feasibility Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Withdrawn
Why Stopped
No recruitment (Feasibility study).
Study Start Date
May 1, 2019 (Actual)
Primary Completion Date
March 8, 2020 (Actual)
Study Completion Date
March 8, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
Canadian Society of Hospital Pharmacists
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This study is to determine the feasibility of an n-of-1, randomized, double blind, placebo controlled case series to examine effects of extended release opioids when used at intervals shorter than recommended by the manufacturer by people with chronic pain.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Pain
Keywords
opioid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Model Description
Feasibility study of an n-of-1, within-subject, crossover, randomized, double blind, placebo controlled case series
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Shortened interval extended release opioid
Arm Type
Active Comparator
Arm Description
Extended release opioid, individualized total daily dose, dosing intervals less than every 12 hours.
Arm Title
Standard interval extended release opioid
Arm Type
Active Comparator
Arm Description
Extended release opioid, individualized total daily dose, dosing intervals every 12 hours
Intervention Type
Drug
Intervention Name(s)
Extended Release Opioid Formulation, Shortened Intervals
Other Intervention Name(s)
Hydromorphone extended release, HydromorphContin, Oxycodone controlled release, morphine sulphate sustained release, morphine slow release
Intervention Description
Extended release opioid, individualized total daily dose, dosing interval is less than every 12 hours
Intervention Type
Drug
Intervention Name(s)
Extended Release Opioid Formulation, Standard intervals
Other Intervention Name(s)
Hydromorphone extended release, HydromorphContin, Oxycodone controlled release, Morphine sulphate sustained release, morphine slow release
Intervention Description
Extended release opioid, individualized total daily dose, dosing interval is every 12 hours
Intervention Type
Drug
Intervention Name(s)
Placebo oral tablet
Other Intervention Name(s)
Placebo (for Extended release opioid)
Intervention Description
Lactose pill manufactured to mimic extended release opioid formulation
Primary Outcome Measure Information:
Title
Percentage of participants who complete both treatment periods and have evaluable Patient Global Impression and pharmacokinetic data
Description
Feasibility outcome
Time Frame
8 months
Secondary Outcome Measure Information:
Title
Patient Global Impression of Change
Description
Single-item rating by subjects of their improvement with treatment on a 7-point scale that ranges from the lowest rating of 1= 'very much improved' to the highest rating of 7= 'very much worse'. Higher values are considered to be a better outcome.
Time Frame
3 weeks
Title
Numerical Pain Rating Scale
Description
A measure of pain intensity. Ten point scale with a minimum of "0"= no pain to a maximum of "10" = worst pain imaginable. Higher scores represent a worse outcome.
Time Frame
3 weeks
Title
Brief Pain Inventory (Short Form)
Description
An inventory of questions about pain, including a pain diagram, pain intensity rating subscales and pain interference rating subscales. The four pain intensity rating subscales are "pain at worst", "pain at least", "pain on average" and "pain right now". These are 10-point scales with a minimum of "0" =no pain, and a maximum of "10"= pain as bad as you can imagine", where higher scores are worse. Pain intensity subscales can be combined as an average on the same scale of 0-10. The eight pain interference subscales measuring interference on general activity, mood, walking ability, work, relations with other people, sleep, enjoyment of life, are 10-point subscales which range a minimum of "0" = pain does not interfere, to a maximum of "10"=pain completely interferes with the item. Higher scores are worse outcomes. Pain interference subscales may be combined as an total score out of 80, or divided by eight to get an average of pain interference on the scale of 0-10.
Time Frame
3 weeks
Title
Subjective Opioid Withdrawal Scale
Description
A self-administered scale for grading 16 opioid withdrawal symptoms on a scale of '0' meaning 'not at all' to '4' meaning 'extremely'. Higher numbers are worse outcomes.
Time Frame
3 weeks
Title
Addiction Research Centre Inventory (ARCI) - short form
Description
The short version of the ARCI is a well-validated, standardized, self-report questionnaire of 49 "true-false" items and is used to differentiate subjective effects of drugs. True = 1, False = 0, responses to selected items are added for scores on different scales. Three of the scales are pertinent to opioid abuse liability: MBG (morphine-benzedrine group), a measure of euphoria, minimum = 0, and a maximum = 16); PCAG (pentobarbital-chlorpromazine-alcohol group) a measure of sedation, minimum =0, maximum=15; LSD (lysergic acid diethylamide scale) a measure of dysphoric and psychotomimetic changes, minimum=0, maximum =14. Higher scores are worse outcomes.
Time Frame
8 hours
Title
Profile of Mood States
Description
A widely used, self-reported questionnaire for assessing drug-induced changes in mood. It has 72 adjectives and phrases describing feelings people have, and ask for the user to describe "how you are feeling right now" on a 5 point scale of descriptives: with a minimum value = 0 "Not at all", to a maximum value of 4= "extremely". Total mood disturbance is calculated by adding the results of the 6 subscales, and then subtracting the vigor -activity subscale (range 0-200). Subscales (six) are calculating by adding specific items: tension-anxiety (9 items, range 0-36), depression (15 items, range 0-60), anger-hostility (12 items, range 0-48), vigor-activity (8 items, range 0-32), fatigue (7 items, range 0-28), confusion-bewilderment (7 items, range 0-28).
Time Frame
8 hours
Title
Visual analogue scale - liking/high
Description
Visual analog scales are 100mm lines, anchored at the ends by opposing adjectives (e.g. like-dislike). "Like" is at the minimum, 0mm mark, "dislike" is at the maximum, 100mm mark. Subjects are instructed to rate how they feel along a continuum by making a mark along the line. The measurement of drug liking is considered to be one of the most sensitive and reliable assessments of the likelihood of abuse of a drug. "Liking" and "High" at the 100mm marks would be considered worse outcomes in terms of likelihood of abuse of a substance.
Time Frame
8 hours
Title
Serum opioid concentrations
Description
Serum opioid concentrations at 0,30 mins, 1,2,3,4,5,6 hours post-dose
Time Frame
6 hours
Title
Peak plasma concentration (Cmax)
Description
The maximum concentration achieved post dose
Time Frame
6 hours
Title
Time to peak plasma concentration (Tmax)
Description
Time that peak plasma concentration occurs post-dose
Time Frame
6 hours
Title
Area under the plasma concentration versus time curve (AUC)
Description
Calculated area under the plasma concentration versus time curve, which describes exposure to the drug.
Time Frame
24 hours
Title
Abuse liability quotient (AQ)
Description
The peak plasma concentration (Cmax) divided by the time to peak plasma concentration, which describes a calculation of the average rate of increase in plasma concentration over the interval between treatment administration and the time of peak plasma concentration.
Time Frame
6 hours
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
>18 years old
willing and capable to give written informed consent
diagnosis of chronic pain (> 3 months)
current prescription for oxycodone controlled release or hydromorphone controlled release or morphine sustained release for pain
Using extended release opioids at intervals less than 12 hours/ more than twice daily
Exclusion Criteria:
ongoing acute pain episode
use of immediate release opioids that contribute to more than 20% of their total daily opioid dose
total daily morphine equivalent dose >400mg
actively tapering their opioid dose
use of multiple extended release opioid products
unstable psychological diagnosis (using the Psychosocial Screening Interview Guide)
outstanding or planned litigation related to pain
pregnancy or lactation in women
history of coronary artery disease
active tapering or titration of benzodiazepines or cannabinoids
positive urine drug screen for amphetamines, barbiturates, cocaine, methamphetamine, methadone, phencyclidine, propoxyphene or unexpected opioids or benzodiazepines
using M-Eslon
using long acting hydromorphone
using Kadian
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Furlan, MD, PhD
Organizational Affiliation
Principal Investigator
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2A2
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
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Dosing Intervals of Opioid Medication for Chronic Pain
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