Cognitive Function and Addiction Under Opioid Tapering

December 1, 2017 updated by: Per Sjogren, Rigshospitalet, Denmark

Cognitive Function and Addiction in Patients With Chronic Pain Under Opioid Tapering in a Multidisciplinary Pain Treatment

This study evaluates the effects of opioid dose reduction in the treatment of chronic pain in adults. Participants were divided in two groups: 1) patients that reduced opioid dose and 2) patients that kept the same opioid dose for six months.

Study Overview

Status

Status

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

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.

Detailed Description

BACKGROUND The indications for initiating long-term opioid treatment for chronic non-cancer pain are often unclear and may be associated with poor outcomes and problematic use. Few available studies demonstrated that opioids do not provide advantages regarding pain control, quality of life and functional capacity in this population and may have numerous serious adverse effects and consequences.

AIMS

This study aimed at:

  1. evaluating the feasibility of a opioid tapering off program to patients with chronic pain,
  2. investigating the influence of opioid tapering off on cognitive function, pain, symptoms of opioid withdrawal, anxiety , depression, and health related quality of life,
  3. investigating the prevalence of addiction in chronic pain patients in a long-term treatment,
  4. determining the predictive value of the Pain Medication Questionnaire (PMQ) in patients with chronic pain,
  5. investigating how opioid tapering off influences PMQ.

METHODS

Study design

This is a prospective, single centre, open-label, parallel-group randomized controlled trial (1:1) conducted at the Multidisciplinary Pain Centre of Rigshospitalet, Copenhagen University Hospital, Denmark.

Two phases with nine assessments were planned. The Phase 1 was the stabilization phase and consisted of two assessments: the first assessment (baseline) was done when patients were admitted to the pain centre and the second assessment was done when medical treatment was considered stable for at least three weeks (stable dose levels and regular intervals). In the following patients went through Phase 2 and were randomized to receive the intervention (Taper off Group) or continue the same stable treatment (Control Group). Seven assessments were planned to this phase: third and fourth assessments were done in intervals of two to three weeks and the following assessments (fifth to ninth) with intervals of one month in between.

Intervention

The taper-off intervention consisted of a reduction of 10% of the daily opioid dose every 1-2 weeks until discontinuation of opioid treatment for up to six months. Clonidine use (25mg - 150mg/day) was allowed in cases of opioid withdrawal symptoms, according to medical prescription.

Analysis

Statistical analysis will be performed to compare baseline characteristics between groups (patients that complete the study vs. patients that dropped out and intervention vs. control group). Comparative analysis of primary and secondary outcomes between groups will also be performed to identify significant differences associated with the intervention.

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

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
75

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 3

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:

  • age 18 years old or more
  • at least seven years of schooling
  • pain duration of at least six months,
  • treatment with oral opioids for more than three months
  • daily opioid dose ≥ 60 mg of oral morphine equivalent

Exclusion Criteria:

  • not fluent in Danish language
  • cancer disease
  • poor general health condition
  • pregnancy, dementia
  • encephalopathy
  • brain damage
  • cranial base trauma
  • enrolled in other studies

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: Parallel Assignment
  • Masking: None (Open Label)

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.
Experimental: Taper off
Decrease of opioid daily dose until discontinuation for up to six months.
Drug: Opioids taper off
Decrease of 10% of opioid daily dose every one to two weeks until discontinuation for up to six months.
Other Names:
  • Morphine, oxycodone, metadone, fentanyl, tramadol
Active Comparator: Control Group
No changes on opioids and adjuvant medication for up to six months.
Drug: Opioid stable treatment
No changes on prescribed opioids and adjuvant medication for the next six months

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
Cognitive function - sustained attention
Time Frame: Through study completion up to 4 years.
EKHO, computer program that registers the continuous reaction time to respond to the emission of a sound signal. Scores were summarized in milliseconds using 10th (fastest values), 50th and 90th (slowest values) percentiles. More prolonged times mean worse performance.
Through study completion up to 4 years.
Cognitive function - psychomotor speed
Time Frame: Through study completion up to 4 years.
Finger Tapping Test, a mechanical device with a key attached was used to record the number of taps. Score was calculated by the numbers of taps, considering the average of each hand and the differences between hands. Higher scores mean better performance.
Through study completion up to 4 years.
Cognitive function - working memory
Time Frame: Through study completion up to 4 years.
Digit Span Test, subjects should repeat orally series of numbers of increasing lengths, in forward and backward orders. Scores were calculated separately for forward and backward exercises, considering the number of correct repetitions. Scores range from 0 to 14. Higher scores mean better performance.
Through study completion up to 4 years.
Cognitive function - mental flexibility
Time Frame: Through study completion up to 4 years
Trail Making Test B, numbers and letters written on a paper should be connected in alternated sequence and increasing order. Score was calculated by the total time spent to correctly conclude the test (seconds). Shorter time mean better performance.
Through study completion up to 4 years
Cognitive function - mental state
Time Frame: Through study completion up to 4 years.
Mini Mental State Examination, measures orientation to time and place, registration of words, attention, calculation, and word recall, as well as language and visual construction. Total scores range from 0 to 30; scores below 27 were considered indicative of cognitive dysfunction.
Through study completion up to 4 years.
Risk of opioid misuse
Time Frame: Through study completion up to 4 years.
Pain Medication Questionnaire, 26 items responded on a 5-point Likert format scale. Scores range from 0 to 104, higher score means higher risk of opioid misuse. Scores equal or above 22 were considered indicative of risk for opioid addiction.
Through study completion up to 4 years.

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
Pain intensity
Time Frame: Through study completion up to 4 years.
Verbal numerical scale from 0=no pain to 10= worst pain, to assess pain right now and average pain.
Through study completion up to 4 years.
Sleep
Time Frame: Through study completion up to 4 years.
Number of total hours of sleep in the previous night before assessment
Through study completion up to 4 years.
Rest
Time Frame: Through study completion up to 4 years.
Rest sensation assessed by the question "do you feel rested?". Answers were categorized as yes or no.
Through study completion up to 4 years.
Quality of life
Time Frame: Through study completion up to 4 years.
RAND 36-Item Short Form Health Survey version 1.0., 36 items distributed in 8 scales: physical functioning, bodily pain, role limitations due to physical health, role limitations due to emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Each item was scored on a 0 to 100 range. Items in the same scale were averaged together to create the 8 scale scores. A high score defines a more favorable health state.
Through study completion up to 4 years.
Depression and anxiety
Time Frame: Through study completion up to 4 years.

Hospital Anxiety and Depression Scale, self-assessment about the last week. It has 14 items divided in anxiety subscale and depression subscale with seven items each one.The maximum score for each scale is 21; cut-off scores for each scale were 8 to 10 for possible and 11 or higher for probable presence of mood disorder.

A clinical judgment was also done by the pain specialist physician (possible answers were yes or no)
Through study completion up to 4 years.
Objective symptoms of opioid withdrawal
Time Frame: Through study completion up to 4 years.
Objective Opiate Withdrawal Scale, 13 physically observable signs, rated present or absent that reflected common motoric and autonomic manifestations of opiate withdrawal: yawning, rhinorrhea, piloerection, perspiration, lacrimation, mydriasis, hands tremors, hot and cold flashes (shivering), restlessness (frequent shifts of position), vomiting. muscle twitches, abdominal cramps, and anxiety. Scores range from 0 to 13, higher scores mean more opioid withdrawal symptoms.
Through study completion up to 4 years.
Subjective symptoms of opioid withdrawal
Time Frame: Through study completion up to 4 years.
Subjective Opiate Withdrawal Scale, self-assessment, 16 items: motoric, autonomic, gastrointestinal, and musculoskeletal opiate withdrawal symptoms and indirectly related psychological symptoms, like anxiety and craving. Answers are scored from 0 to 4 based on how patient is feeling at the time of assessment. Scores range is 0-64, higher scores mean more opioid withdrawal symptoms.
Through study completion up to 4 years.
Addiction - Portnoy's Criteria
Time Frame: Through study completion up to 4 years.
Classification according to Portnoy's Criteria (psychological dependence, evidence of compulsive drug use, and evidence of a group of associated behaviors). Subjects were classified in addict and non-addict.
Through study completion up to 4 years.
Addiction - International Classification of Diseases -10.
Time Frame: Through study completion up to 4 years.
Diagnostic criteria according to the International Classification of Diseases -10. Subjects should present at least three symptoms associated with addiction in the least month or several times within a year to be considered addict.
Through study completion up to 4 years.

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.
Rigshospitalet, Denmark

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.
The Ministry of Science, Technology and Innovation, Denmark
Hørslev-Fonden

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: Per Sjøgren, DMSc, Rigshospitalet, Denmark
  • Principal Investigator: Jette Højsted, MD, Rigshospitalet, Denmark

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.
February 2, 2009

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.
December 1, 2014

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.
December 1, 2014

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).
November 22, 2017

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.
December 1, 2017

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.
December 7, 2017

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.
December 7, 2017

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.
December 1, 2017

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.
December 1, 2017

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.
  • H-B-2008-061

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

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.

Clinical Trials on Chronic Pain

Clinical Trials on Opioids taper off

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings