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Dosing Intervals of Opioid Medication for Chronic Pain

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ClinicalTrials.gov Identifier: NCT04132011
Recruitment Status : Withdrawn (No recruitment (Feasibility study).)
First Posted : October 18, 2019
Last Update Posted : March 27, 2020
Sponsor:
Collaborator:
Canadian Society of Hospital Pharmacists
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE October 2, 2019
First Posted Date  ICMJE October 18, 2019
Last Update Posted Date March 27, 2020
Actual Study Start Date  ICMJE May 1, 2019
Actual Primary Completion Date March 8, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 17, 2019)
Percentage of participants who complete both treatment periods and have evaluable Patient Global Impression and pharmacokinetic data [ Time Frame: 8 months ]
Feasibility outcome
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 17, 2019)
  • Patient Global Impression of Change [ Time Frame: 3 weeks ]
    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 [ Time Frame: 3 weeks ]
    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) [ Time Frame: 3 weeks ]
    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 [ Time Frame: 3 weeks ]
    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 [ Time Frame: 8 hours ]
    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 [ Time Frame: 8 hours ]
    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 [ Time Frame: 8 hours ]
    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 [ Time Frame: 6 hours ]
    Serum opioid concentrations at 0,30 mins, 1,2,3,4,5,6 hours post-dose
  • Peak plasma concentration (Cmax) [ Time Frame: 6 hours ]
    The maximum concentration achieved post dose
  • Time to peak plasma concentration (Tmax) [ Time Frame: 6 hours ]
    Time that peak plasma concentration occurs post-dose
  • Area under the plasma concentration versus time curve (AUC) [ Time Frame: 24 hours ]
    Calculated area under the plasma concentration versus time curve, which describes exposure to the drug.
  • Abuse liability quotient (AQ) [ Time Frame: 6 hours ]
    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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Dosing Intervals of Opioid Medication for Chronic Pain
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Feasibility study of an n-of-1, within-subject, crossover, randomized, double blind, placebo controlled case series
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Chronic Pain
Intervention  ICMJE
  • Drug: Extended Release Opioid Formulation, Shortened Intervals
    Extended release opioid, individualized total daily dose, dosing interval is less than every 12 hours
    Other Names:
    • Hydromorphone extended release
    • HydromorphContin
    • Oxycodone controlled release
    • morphine sulphate sustained release
    • morphine slow release
  • Drug: Extended Release Opioid Formulation, Standard intervals
    Extended release opioid, individualized total daily dose, dosing interval is every 12 hours
    Other Names:
    • Hydromorphone extended release
    • HydromorphContin
    • Oxycodone controlled release
    • Morphine sulphate sustained release
    • morphine slow release
  • Drug: Placebo oral tablet
    Lactose pill manufactured to mimic extended release opioid formulation
    Other Name: Placebo (for Extended release opioid)
Study Arms  ICMJE
  • Active Comparator: Shortened interval extended release opioid
    Extended release opioid, individualized total daily dose, dosing intervals less than every 12 hours.
    Interventions:
    • Drug: Extended Release Opioid Formulation, Shortened Intervals
    • Drug: Placebo oral tablet
  • Active Comparator: Standard interval extended release opioid
    Extended release opioid, individualized total daily dose, dosing intervals every 12 hours
    Interventions:
    • Drug: Extended Release Opioid Formulation, Standard intervals
    • Drug: Placebo oral tablet
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: March 25, 2020)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 17, 2019)
6
Actual Study Completion Date  ICMJE March 8, 2020
Actual Primary Completion Date March 8, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04132011
Other Study ID Numbers  ICMJE 17-6180
Has Data Monitoring Committee No
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Health Network, Toronto
Study Sponsor  ICMJE University Health Network, Toronto
Collaborators  ICMJE Canadian Society of Hospital Pharmacists
Investigators  ICMJE
Principal Investigator: Andrea Furlan, MD, PhD Principal Investigator
PRS Account University Health Network, Toronto
Verification Date September 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP