Clinical trial NCT06063902: Long-Term Opioid Therapy in Chronic Non-Cancer Pain: Risks and Benefits
Official title: Long-Term Opioid Therapy in Chronic Non-Cancer Pain: Risks and Benefits - A Prospective Cohort Study of Patients Treated in Specialized Pain Care
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Chronic Non-Cancer Pain
Opioid Use Disorder
Keywords: Chronic pain
Chronic primary pain
Analgesics
Opioid
Opioid-use disorder
Work Ability
Health-related quality of life
Opioid-related risk behavior
Pain
Activity
Opioid-related complications
Lead sponsor: Uppsala University
Sponsor class: OTHER
First posted: 2023-10-03
Enrollment: 1000
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with moderate to severe CNCP referred to secondary and tertiary pain care at the Uppsala University Hospital.

Brief summary: The study investigates long-term opioid treatment in patients with chronic non-cancer pain (CNCP). The study aims to prospectively identify predictive factors for work ability and for developing opioid use disorder (according to DSM-5) as well as predictive factors for pain, activity, and health-related quality of life.

It is hypothesized that certain biopsychosocial factors mapped in this study predict patterns of opioid use and the risk for developing OUD for patients with CNCP on long-term opioid therapy. Further, it is hypothesized that certain biopsychosocial factors mapped in this study predict the chance of improved work ability and other treatment benefits of long term opioid therapy in patients with CNCP.

Detailed description: Chronic pain affects nearly 20% of the Swedish population. Pain from the musculoskeletal system together with psychiatric disorders are the chronic conditions that cost the most for the Swedish health care disability insurance and health care systems. Current knowledge suggests that chronic pain is maintained by changes in the nervous system together with psychological and social factors.

Opioids are known to be effective for acute and post-operative pain, and can be indispensable in palliative treatment of cancer pain. Long-term opioid therapy on the other hand is associated witg several risks, e.g., development of opioid dependence and opioid use disorder (OUD), and other opioid related complications including premature death. Clinical experience, qualitative and quantitative research suggest that some individuals with chronic pain do benefit from long-term opioid therapy in terms of clinical significant pain relief with only a low level of negative side-effects. However, evidence of change in functional outcomes and health related quality of life is ambiguous. Therefore, the role of long-term opioid therapy in chronic pain conditions remains debated and sometimes controversial.

In contrast to the well-established opioid epidemic in the U.S., little is known about the use of prescribed opioids in Sweden, and how this has developed during the last decade. The annual prevalence of opioid prescription did not change much during 2006-2017, but there were significant shifts in choice of opioids, with an increase in strong opioids e.g., oxycodone and morphine. Very little is known about what clinical consequences this shift might lead to.

The U-PAIN cohort study aims to examine patterns of prescribed opioid use, risks of adverse effects of long-term opioid therapy, and benefits of long-term opioid therapy, in a prospective clinical cohort.

The study aims to complete a broad bio-psycho-social characterization of the participants relevant to chronic pain. The study participants are followed over 5 years in order to study trajectories for patterns of opioid use, and predictive factors for opioid use disorder, work ability, pain severity and interference, and health-related quality of life.

At baseline, participants will be classified into 4 groups based on their current use of opioids:

1. No use
2. Short-term or intermittent use Criteria: short-term use defined as regular use of opioids for \< 3 months or intermittent use as dosing up to 10 days/months (independent of time frame).
3. Long-term use with low to moderate doses Criteria: use of opioids for more \> 3 months, more the 10 days/month and mean daily dose \< 40 mg (oral morphine milligram equivalent dose (MEE) defined as low dose. Mean daily dose 40-100 mg MEE defined as high dose.
4. Long-term use with high doses Criteria: use of opioids for \> 3 months. More than 100 mg MEE.

Main research questions for the cohort study are:

1. What characterizes patients without opioid use disorder at baseline compared to patients with mild, moderate or severe opioid use disorder respectively at baseline?
2. What variables predict their future:

   1. Patterns of opioid use and substance use disorder?
   2. Work ability, activity interference, quality of life and pain?

Potential predictors and co-variates include: (1) Individual factor and demographic variables (2) Pain characteristics, (3) Psychiatric co-morbidity and susceptibility for OUD, (3) Cognitive-behavioral variables, and (4) Physical functioning.

The objective is to identify the most salient predictors from each group and combine them into a final model with the best goodness of fit.

The four groups concerning patterns of opioid use will be statistically compared regarding key outcomes at baseline (opioid use disorders, work ability, activity interference, pain and HQoL)) by use of t-tests and chi-square tests. Logistic regression analyses will be applied for the study of predictors of opioid use, OUD, work ability, activity interference and pain. The dependent variables, e.g. OUD/no OUD will be regressed towards hypothetic predictors, grouped as described earlier, to end up with a final model including the most salient predictors from each group of variables. Multivariate regression models will be considered for continuous dependent variables.

In addition this clinical cohort will be open for other studies after ethical vetting, i.e. the cohort is unique and could contribute to further understanding of this population and hence should be open for further research.

Eligibility criteria: Inclusion Criteria:

1. Referral for a first visit to the Pain Centre of Uppsala University Hospital. The following
2. Competent in Swedish
3. Chronic Non-Cancer Pain (pain \> 90 days)

Exclusion Criteria:

1. In active cancer treatment/Cancer-related pain
2. In palliative care
3. Need for interpreter
4. Cognitive impairment of magnitude that will prevent completion of study or ability to give informed consent

Primary outcomes:
measure: Characterization and changes in opioid use disorder
timeFrame: Baseline, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Changes in work ability
timeFrame: Baseline, 1 year, 2 years, 3 years, 4 years, 5 years
Secondary outcomes:
measure: Changes and patterns of opioid use (type of opioid, dose, and duration)
timeFrame: Baseline, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Changes in pain severity and pain interference: The Brief Pain Inventory short-form (BPI-SF)
timeFrame: Baseline, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Changes in health related quality of life: EQ-5D-5L
timeFrame: Baseline, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Depressive symptoms
timeFrame: Baseline
measure: Generalised Anxiety Disorder
timeFrame: Baseline
measure: Sleep
timeFrame: Baseline
measure: Pain self-efficacy
timeFrame: Baseline
measure: Experienced injustice
timeFrame: Baseline
measure: Fear of movement and reinjury
timeFrame: Baseline
measure: Catastrophizing - The Pain Catastrophizing Scale (PCS) - Swedish version.
timeFrame: Baseline
measure: Changes in life habits
timeFrame: Baseline, 1 year, 2 years, 3 years, 4 years, 5 years
measure: Alcohol Use
timeFrame: Baseline
measure: Illicit drug use
timeFrame: Baseline
measure: Pain classification
timeFrame: Baseline
measure: Personality traits
timeFrame: Baseline
measure: Attention-deficit hyperactivity disorder (ADHD) symptoms
timeFrame: Baseline
measure: Life-time experience of traumatic events
timeFrame: Baseline
measure: Walk speed
timeFrame: Baseline
measure: Balance
timeFrame: Baseline
measure: Substance use and substance use disorder
timeFrame: Baseline
measure: Explorative identification of change in biomarkers
timeFrame: Baseline
measure: Experienced effect of treatment/Global goal achievement
timeFrame: 1 year
measure: Experienced effect of treatment/Global goal achievement
timeFrame: 2 year
measure: Experienced effect of treatment/Global goal achievement
timeFrame: 3 year
measure: Experienced effect of treatment/Global goal achievement
timeFrame: 4 year
measure: Experienced effect of treatment/Global goal achievement
timeFrame: 5 year
Other outcomes:
measure: Sick-leave
timeFrame: Baseline
measure: Sick-leave
timeFrame: 1 year
measure: Sick-leave
timeFrame: 2 year
measure: Sick-leave
timeFrame: 3 year
measure: Sick-leave
timeFrame: 4 year
measure: Sick-leave
timeFrame: 5 year
measure: Prescribed drugs
timeFrame: Baseline
measure: Prescribed drugs
timeFrame: 1 year
measure: Prescribed drugs
timeFrame: 2 year
measure: Prescribed drugs
timeFrame: 3 year
measure: Prescribed drugs
timeFrame: 4 year
measure: Prescribed drugs
timeFrame: 5 year
Locations:
city: Uppsala
country: Sweden
facility: Uppsala Univeristy Hospital
Study officials:
affiliation: Uppsala University
name: Pernilla Åsenlöf, Professor
role: PRINCIPAL_INVESTIGATOR
References: