Clinical trial NCT03365817: Cognitive Function and Addiction Under Opioid Tapering
Official title: Cognitive Function and Addiction in Patients With Chronic Pain Under Opioid Tapering in a Multidisciplinary Pain Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Pain
Opioid Use
Keywords: cognitive function
opioid dependence
opioid withdrawal
quality of life
side effect
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: The Ministry of Science, Technology and Innovation, Denmark
name: Hørslev-Fonden
First posted: 2017-12-07
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Random assignment
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Cognitive function - sustained attention
timeFrame: Through study completion up to 4 years.
measure: Cognitive function - psychomotor speed
timeFrame: Through study completion up to 4 years.
measure: Cognitive function - working memory
timeFrame: Through study completion up to 4 years.
measure: Cognitive function - mental flexibility
timeFrame: Through study completion up to 4 years
measure: Cognitive function - mental state
timeFrame: Through study completion up to 4 years.
measure: Risk of opioid misuse
timeFrame: Through study completion up to 4 years.
Secondary outcomes:
measure: Pain intensity
timeFrame: Through study completion up to 4 years.
measure: Sleep
timeFrame: Through study completion up to 4 years.
measure: Rest
timeFrame: Through study completion up to 4 years.
measure: Quality of life
timeFrame: Through study completion up to 4 years.
measure: Depression and anxiety
timeFrame: Through study completion up to 4 years.
measure: Objective symptoms of opioid withdrawal
timeFrame: Through study completion up to 4 years.
measure: Subjective symptoms of opioid withdrawal
timeFrame: Through study completion up to 4 years.
measure: Addiction - Portnoy's Criteria
timeFrame: Through study completion up to 4 years.
measure: Addiction - International Classification of Diseases -10.
timeFrame: Through study completion up to 4 years.
Other outcomes:
Locations:
Study officials:
affiliation: Rigshospitalet, Denmark
name: Per Sjøgren, DMSc
role: PRINCIPAL_INVESTIGATOR
affiliation: Rigshospitalet, Denmark
name: Jette Højsted, MD
role: PRINCIPAL_INVESTIGATOR
References: