Tapering From Long-term Opioid Therapy in Chronic Pain Population. Randomized Controlled Trial With 12 Months Follow up (TOPIO)

Tapering of Prescribed Opioids in Patients With Long-term Non-malignant Pain - Efficacy and Effects on Pain, Pain Cognitions, and Quality of Life (TOPIO): a Study Protocol for a Randomized Controlled Clinical Trial With a 12 Month Follow-up

This randomized controlled study compares tapering of long-term opioid therapy in a population with chronic non-cancer pain with control group constituted of waiting list. Half of participants receives intervention at baseline and the other half are controls but receives intervention after 4 months. Ethical approval to follow up excluded participants denying tapering at baseline.

Study Overview

• Status: Recruiting
• Conditions: Chronic Pain; Substance Use Disorders; Opioid Use; Opioid Withdrawal; Analgesics, Opioid
• Intervention / Treatment: Behavioral: Tapering

Detailed Description

Chronic non-cancer pain is a major problem in society and a common cause to seek health care. The suffering is complex as it, besides pain, often includes psychological symptoms and may decrease the ability to participate in work life. Pharmacological treatments have limited possibilities to ease suffering. Opioids used in this population have evidence to ease pain and to some extent increase physical ability when used in limited treatment periods and in selected patients. Medium to long-term opioid therapy, extended beyond three months, lack evidence of easing pain or increase physical ability.

The current study is conducted on three specialized pain care units (Skane University Hospital; Lund, Sahlgrenska University Hospital Gothenburg and University Hospital, Linkoeping) and aims at taper long-term opioid therapy with support from physician and nurse and study the effects of tapering.

Method: Randomized controlled study, without concealment. Waiting-list constitutes the control-group. Intervention means tapering with a motivated patient. Follow up at four and twelve months.

Primary end-point: collected opioid prescriptions registered in The National Board of Health and Welfare registry expressed in milligram of morphine equivalent.

Secondary end-point: Data will be retrieved from the Swedish Quality Registry for Pain Rehabilitation. The database contains participants' self-report of variables measuring the impact of rehabilitation on depressive symptoms, anxiety, rating of pain and acceptance to pain. Assessments are made prior to, at the end of and one year after discharge of the rehabilitation program.

As denying tapering or participation is shown to be as common as decision to taper drugs at baseline an extended ethical approval was acquired also retrospective. This approval covers obtaining collected prescribed medication and prescribed opioid replacement therapy (Buprenorphine or Methadone) after one year. The study may describe the excluded population better this way.

• Study Type: Interventional
• Enrollment (Anticipated): 140
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Henrik Grelz, MD; Phone Number: +46703002832; Email: henrik.grelz@med.lu.se
• Study Contact Backup: Name: Åsa Ringqvist, MD, PhD; Email: Asa.Ringqvist@skane.se

Study Locations

• Sweden
  • Skåne
    • Lund, Skåne, Sweden, 22100
      • Recruiting
      • Lund University Hospital
      • Contact: Henrik Grelz, MD; Phone Number: +4646172289; Email: henrik.grelz@med.lu.se
      • Contact: Åsa Ringqvist, MD PhD; Email: Asa.Ringqvist@skane.se
      • Principal Investigator: Henrik Grelz, MD
      • Sub-Investigator: Åsa Ringqvist, MD PhD
      • Sub-Investigator: Marcelo Rivano Fischer, PhD
  • Västra Götaland
    • Gothenburg, Västra Götaland, Sweden
      • Recruiting
      • Paincentre Sahlgrenska University Hospital
      • Contact: Cecilia Grinsvall, MD PhD; Email: cecilia.grinsvall@vgregion.se
  • Östergötland
    • Linköping, Östergötland, Sweden
      • Recruiting
      • Pain and rehabilitation centre Linköping University Hospital
      • Contact: Emmanuel Bäckryd, MD PhD; Email: emmanuel.backryd@liu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A long-term opioid therapy with daily intake due to chronic pain condition, by prescription. Willing to enter an intervention aiming at taper opioid therapy.

Exclusion Criteria:

No daily intake of opioids. Shorter duration of opioid therapy than 3 months. Repeated intake of non-prescribed opioids or other illegal drugs. Refusal to perform drug-screening Perceived medical risks of waiting with tapering of opioids (e.g: raising opioid doses after acute pancreatitis caused by excessive alcohol intake or kidney disease stage 4-5 in combination with excessive alcohol intake and high doses of opioids).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Intervention; Receives tapering of opioid dose at baseline	Behavioral: Tapering; Tapering with follow up by nurse at weekly basis in beginning of tapering. Tapering in an outpatient setting. Follow-up to doctor after four months.
NO_INTERVENTION: Control; Waiting-list. Receives tapering after 4 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid consumption	Data retrieved from National Boars of Health and Welfare, collected prescribed opioid drugs	12 months
Opioid consumption	Self reported consumption	4 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Numeric Pain Rating Scale (NPRS)	NPRS was used to capture the patient's level of pain intensity. Patients rate their average level of pain the last week. The 11-point scale spans from the left with the phrase "no pain" i.e. 0 and on the right to the phrase "worst imaginable pain" i.e. 10.	12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospital Anxiety and Depression scale (HADS)	HADS was constructed for patients in medical settings. It entails 14-item measures of anxiety (7 items) and depression (7 items) symptoms over the course of a week. Items are rated on a four-point scale (0 = not all; 3 = very often) and the anxiety and depression subscales range from 0 to 21. Higher scores indicate greater severity.	12 months
Tampa Scale for Kinesiophobia (TSK)	The TSK employs a 4-point Likert scale, with scoring options ranging from 1 (strongly disagree) to 4 (strongly agree) and encompasses 17 items related to pain, fear of movement and re-injury. The total score of the original 17-item version ranges between 17 and 68, with a higher score indicating a higher degree of Kinesiophobia.	12 months
Pain Catastrophizing Scale (PCS)	The PCS comprises 13 items that are rated from 0 to 4 with the endpoints 0 ("Never") to 4 ("All the time") and was constructed to assess pain-related catastrophizing (48). Catastrophizing include three factors: (a) Helplessness i.e. perceived helplessness in situations when pain is present (six items); (b) Rumination, concerning vigilance toward the pain experience (four items) ; and (c) Magnification i.e. the tendency to magnify the threat value of pain (three items). The total score ranges from 0-52 points with a higher score indicating a higher degree of catastrophizing.	12 months
Chronic Pain Acceptance Questionnaire (CPAQ-8)	Pain acceptance measures two main classes of behaviors represented by respective subscales: Activity Engagement (score range: 0-24), and Pain Willingness (inverted score range: 0-24). The items are rated from 0 (never true) to 6 (always true) and higher values indicate higher acceptance to chronic pain.	12 months
Perceptions of health	RAND-36 is a modern translation of SF-36. RAND-36 encompasses questions from eight domains (subscales) i.e. physical functioning (PF), role physical (RP), bodily pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE) and mental health (MH). The scores are subsequently transformed in a standardized way into a 0-100 scale where higher scores indicate better health.	12 months

Collaborators and Investigators

• Sponsor: Lund University Hospital
• Collaborators: Lund University; Sahlgrenska University Hospital, Sweden; University Hospital, Linkoeping
• Investigators: Study Chair: Åsa IRingqvist, MD, PhD, Lund University

Publications and helpful links

General Publications

• Henrik G, Patrik M, Anders H, Ulf J, Marcelo RF, Asa R. Tapering of prescribed opioids in patients with long-term non-malignant pain (TOPIO)-efficacy and effects on pain, pain cognitions, and quality of life: a study protocol for a randomized controlled clinical trial with a 12-month follow-up. Trials. 2021 Jul 28;22(1):503. doi: 10.1186/s13063-021-05449-5.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 22, 2018
• Primary Completion (ANTICIPATED): March 20, 2023
• Study Completion (ANTICIPATED): March 20, 2024

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (ACTUAL): April 2, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 12, 2022
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Pain; Neurologic Manifestations; Substance-Related Disorders; Chronic Pain
• Other Study ID Numbers: 7206093515

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