Chronic PainPhase 3NCT03365817
Cognitive Function and Addiction Under Opioid Tapering
A Phase 3 study testing Opioids taper off and Opioid stable treatment in people with Chronic Pain and Opioid Use, run by Copenhagen University Hospital, Rigshospitalet.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Pain, Opioid Use
- What is being tested?
- Opioids taper off and Opioid stable treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- No sites listed yet
- Study dates
- 2 Feb 2009to 1 Dec 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- not fluent in Danish language
- cancer disease
- poor general health condition
- pregnancy, dementia
- encephalopathy
- brain damage
- cranial base trauma
- enrolled in other studies
About this study
Official title: 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.
Read the 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:
- evaluating the feasibility of a opioid tapering off program to patients with chronic pain,
- investigating the influence of opioid tapering off on cognitive function, pain, symptoms of opioid withdrawal, anxiety , depression, and health related quality of life,
- investigating the prevalence of addiction in chronic pain patients in a long-term treatment,
- determining the predictive value of the Pain Medication Questionnaire (PMQ) in patients with chronic pain,
- 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.
- Conditions
- Chronic Pain, Opioid Use
- Being tested
- Opioids taper off, Opioid stable treatment
- Keywords
- cognitive function, opioid dependence, opioid withdrawal, quality of life, side effect
- Medical subject headings
- Chronic Pain, Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Opioids taper offDrug
Also called Morphine, oxycodone, metadone, fentanyl, tramadol
Decrease of 10% of opioid daily dose every one to two weeks until discontinuation for up to six months.
Opioid stable treatmentDrug
No changes on prescribed opioids and adjuvant medication for the next six months
| Study group | Role | What they receive |
|---|---|---|
| Taper off | Experimental | Decrease of opioid daily dose until discontinuation for up to six months. Receives: Drug: Opioids taper off |
| Control Group | Active comparator | No changes on opioids and adjuvant medication for up to six months. Receives: Drug: Opioid stable treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive function - sustained attention
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.
Measured: Through study completion up to 4 years.
Cognitive function - psychomotor speed
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.
Measured: Through study completion up to 4 years.
Cognitive function - working memory
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.
Measured: Through study completion up to 4 years.
Cognitive function - mental flexibility
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.
Measured: Through study completion up to 4 years
Cognitive function - mental state
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.
Measured: Through study completion up to 4 years.
Risk of opioid misuse
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.
Measured: Through study completion up to 4 years.
Secondary outcomes (9)
Pain intensity
Verbal numerical scale from 0=no pain to 10= worst pain, to assess pain right now and average pain.
Measured: Through study completion up to 4 years.
Sleep
Number of total hours of sleep in the previous night before assessment
Measured: Through study completion up to 4 years.
Rest
Rest sensation assessed by the question "do you feel rested?". Answers were categorized as yes or no.
Measured: Through study completion up to 4 years.
Quality of life
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.
Measured: Through study completion up to 4 years.
Depression and anxiety
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)
Measured: Through study completion up to 4 years.
Objective symptoms of opioid withdrawal
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.
Measured: Through study completion up to 4 years.
Subjective symptoms of opioid withdrawal
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.
Measured: Through study completion up to 4 years.
Addiction - Portnoy's Criteria
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.
Measured: Through study completion up to 4 years.
Addiction - International Classification of Diseases -10.
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.
Measured: Through study completion up to 4 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2017
- Study start2 Feb 2009
- Primary completion1 Dec 2014
- Study completion1 Dec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Random assignment
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Copenhagen University Hospital, Rigshospitalet
- Sponsor type
- University, hospital or other
- Collaborators
- The Ministry of Science, Technology and Innovation, Denmark, Hørslev-Fonden
- Responsible party
- Principal investigator, Per Sjogren, Copenhagen University Hospital, Rigshospitalet
- Investigators
- Per Sjøgren, DMSc, Principal investigator, Copenhagen University Hospital, RigshospitaletJette Højsted, MD, Principal investigator, Copenhagen University Hospital, Rigshospitalet
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03365817
- Sponsor's protocol ID
- H-B-2008-061
- Status last verified
- Dec 2017
- First submitted
- 22 Nov 2017
- Last updated
- 7 Dec 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cognitive Function and Addiction in Patients With Chronic Pain Under Opioid Tapering in a Multidisciplinary Pain Treatment
- ClinicalTrials.gov ID
- NCT03365817
- Acronym / sponsor ID
- H-B-2008-061
- Conditions
- Chronic Pain, Opioid Use
- Keywords
- cognitive function, opioid dependence, opioid withdrawal, quality of life, side effect
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
- Collaborators
- The Ministry of Science, Technology and Innovation, Denmark, Hørslev-Fonden
- Study start
- 2 Feb 2009 (actual)
- Primary completion
- 1 Dec 2014 (actual)
- Study completion
- 1 Dec 2014 (actual)
- First posted
- 7 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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:
- evaluating the feasibility of a opioid tapering off program to patients with chronic pain,
- investigating the influence of opioid tapering off on cognitive function, pain, symptoms of opioid withdrawal, anxiety , depression, and health related quality of life,
- investigating the prevalence of addiction in chronic pain patients in a long-term treatment,
- determining the predictive value of the Pain Medication Questionnaire (PMQ) in patients with chronic pain,
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Random assignment
| Arm | Type | Receives |
|---|---|---|
| Taper off | Experimental | Drug: Opioids taper offDecrease of opioid daily dose until discontinuation for up to six months. |
| Control Group | Active comparator | Drug: Opioid stable treatmentNo changes on opioids and adjuvant medication for up to six months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (8 listed)
- not fluent in Danish language
- cancer disease
- poor general health condition
- pregnancy, dementia
- encephalopathy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Opioids taper offAlso: Morphine, oxycodone, metadone, fentanyl, tramadolDecrease of 10% of opioid daily dose every one to two weeks until discontinuation for up to six months. | Drug | Taper off |
| Opioid stable treatmentNo changes on prescribed opioids and adjuvant medication for the next six months | Drug | Control Group |
Primary outcome
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.
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.
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.
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.
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.
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.
9 secondary outcomes
Pain intensity
Time frame: Through study completion up to 4 years.
Sleep
Time frame: Through study completion up to 4 years.
Rest
Time frame: Through study completion up to 4 years.
Quality of life
Time frame: Through study completion up to 4 years.
Depression and anxiety
Time frame: Through study completion up to 4 years.
Objective symptoms of opioid withdrawal
Time frame: Through study completion up to 4 years.
Subjective symptoms of opioid withdrawal
Time frame: Through study completion up to 4 years.
Addiction - Portnoy's Criteria
Time frame: Through study completion up to 4 years.
Addiction - International Classification of Diseases -10.
Time frame: Through study completion up to 4 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2017.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Per Sjøgren, DMSc principal investigator
Copenhagen University Hospital, Rigshospitalet
Jette Højsted, MD principal investigator
Copenhagen University Hospital, Rigshospitalet
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Opioids taper off and Opioid stable treatment in people with Chronic Pain and Opioid Use, run by Copenhagen University Hospital, Rigshospitalet.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive function - sustained attention (time frame: Through study completion up to 4 years.). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Dec 2017.