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Dosing Intervals of Opioid Medication for Chronic Pain

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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Recruitment Status : Withdrawn (No recruitment (Feasibility study).)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

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.

Condition or disease Intervention/treatment Phase
Chronic Pain Drug: Extended Release Opioid Formulation, Shortened Intervals Drug: Extended Release Opioid Formulation, Standard intervals Drug: Placebo oral tablet Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
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
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
Actual Study Start Date : May 1, 2019
Actual Primary Completion Date : March 8, 2020
Actual Study Completion Date : March 8, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Chronic Pain

Arm Intervention/treatment
Active Comparator: Shortened interval extended release opioid
Extended release opioid, individualized total daily dose, dosing intervals less than every 12 hours.
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: Placebo oral tablet
Lactose pill manufactured to mimic extended release opioid formulation
Other Name: Placebo (for Extended release opioid)

Active Comparator: Standard interval extended release opioid
Extended release opioid, individualized total daily dose, dosing intervals every 12 hours
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)




Primary Outcome Measures :
  1. Percentage of participants who complete both treatment periods and have evaluable Patient Global Impression and pharmacokinetic data [ Time Frame: 8 months ]
    Feasibility outcome


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. Serum opioid concentrations [ Time Frame: 6 hours ]
    Serum opioid concentrations at 0,30 mins, 1,2,3,4,5,6 hours post-dose

  9. Peak plasma concentration (Cmax) [ Time Frame: 6 hours ]
    The maximum concentration achieved post dose

  10. Time to peak plasma concentration (Tmax) [ Time Frame: 6 hours ]
    Time that peak plasma concentration occurs post-dose

  11. 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.

  12. 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04132011


Locations
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Canada, Ontario
University Health Network
Toronto, Ontario, Canada, M5G 2A2
Sponsors and Collaborators
University Health Network, Toronto
Canadian Society of Hospital Pharmacists
Investigators
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Principal Investigator: Andrea Furlan, MD, PhD Principal Investigator
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Responsible Party: University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT04132011    
Other Study ID Numbers: 17-6180
First Posted: October 18, 2019    Key Record Dates
Last Update Posted: March 27, 2020
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by University Health Network, Toronto:
opioid
Additional relevant MeSH terms:
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Chronic Pain
Pain
Neurologic Manifestations
Morphine
Oxycodone
Analgesics, Opioid
Hydromorphone
Narcotics
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents