Dosing Intervals of Opioid Medication for Chronic Pain

March 25, 2020 updated by: University Health Network, Toronto

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2A2
        • University Health Network

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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 Names:
  • 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: Placebo oral tablet
Lactose pill manufactured to mimic extended release opioid formulation
Other Names:
  • Placebo (for Extended release opioid)
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 slow release
  • Morphine sulphate sustained release

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Percentage of participants who complete both treatment periods and have evaluable Patient Global Impression and pharmacokinetic data
Time Frame: 8 months
Feasibility outcome
8 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
3 weeks
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 weeks
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.
3 weeks
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.
3 weeks
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.
8 hours
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).
8 hours
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 hours
Serum opioid concentrations
Time Frame: 6 hours
Serum opioid concentrations at 0,30 mins, 1,2,3,4,5,6 hours post-dose
6 hours
Peak plasma concentration (Cmax)
Time Frame: 6 hours
The maximum concentration achieved post dose
6 hours
Time to peak plasma concentration (Tmax)
Time Frame: 6 hours
Time that peak plasma concentration occurs post-dose
6 hours
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.
24 hours
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.
6 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Canadian Society of Hospital Pharmacists

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Andrea Furlan, MD, PhD, Principal Investigator

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 8, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 8, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 2, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 17, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 18, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 27, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 25, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17-6180

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

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