Chronic PainNOR-APTNCT04908410
The Norwegian Addiction, Pain and Trauma Study
An observational study of Chronic Pain and Post-traumatic Stress Disorder, run by University Hospital, Akershus at 4 sites in Norway.
Trial summary
In populations with substance use disorders (SUD), there is a high prevalence of chronic pain with various underlying causes. Chronic pain can complicate the treatment of SUD and lead to poorer treatment outcomes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Pain, Post-traumatic Stress Disorder, Substance Use Disorders
- How many people
- 1,650 participants
- Where
- 4 sitesNorway
- Study dates
- 23 Mar 2021to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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
Study population: Patients (ages 18 years - unlimited) in treatment for substance use disorders at outpatient and inpatient treatment centers connected to Akerhus University Hospital or Oslo University Hospital, Norway.
Who may be able to join
- Patient in substance use treatment at a treatment centre under Akershus University Hospital, Oslo University Hospital, Vestfold Hospital or Telemark Hospital.
Who cannot join
- Staff considers the patient to be unable to give informed consent/valid responses on the questionnaire OR staff considers participation to be too stressful/burdensome to the patient. Staff are asked to take the following into consideration when making their assessment:
- Acute withdrawal
- Acute intoxication
- Serious mental health concerns
- Serious physical health concerns
Trial locations and contacts
4 sites in 1 country.
Norway4 sites
Akershus University Hospital
Lørenskog, 0192
Oslo University Hospital
Oslo
Telemark Hospital
Skien
The Hospital in Vestfold
Tønsberg
About this study
In populations with substance use disorders (SUD), there is a high prevalence of chronic pain with various underlying causes. Chronic pain can complicate the treatment of SUD and lead to poorer treatment outcomes. There is a need for a better understanding of the connections and interactions between chronic pain and substance use and dependence.
Further, there is a high prevalence of chronic pain among patients with post-traumatic stress disorder (PTSD). As there is an overlap between populations with SUD and PTSD, taking potentially traumatizing life-experiences and post-traumatic stress symptoms into account can provide a better understanding of chronic pain in populations with SUD.
Read more
The Nor-APT study is a cross-sectional study, recruiting from outpatient and inpatient substance use treatment centres connected to four hospitals. Participants complete a questionnaire about substance/medication use, pain and how pain affect function, stressful life events and post-traumatic stress symptoms. Patients can consent to self-reported data being linked to retrospective and prospective longitudinal data from national demographic and health registries.
The purpose of the study is to contribute to a better understanding and treatment of chronic pain among people with substance use disorders (SUD), and to contribute to the understanding of co-occurring substance use, chronic pain and post-traumatic stress symptoms.
The over-arching research aims are to:
- Describe the prevalence and characteristics of pain for people in need of treatment for substance/medication use/dependence.
II. Describe how the pain affects physical and emotional functioning, and subjective quality of life.
III. Explore any connections between substance/medication use and pain, both what came first and any ways substance/medication use and pain affect each other.
IV. Explore the connection between chronic pain, potentially traumatizing life events and post-traumatic stress symptoms.
- Explore how treatments received and how treatment affects outcomes.
In addition, we will explore whether participants' experiences can be categorized into typical trajectories for how substance use, chronic pain and stressful life events occur and develop over the life span.
Read the detailed description
INTRODUCTION
Chronic pain and substance use
The prevalence of chronic pain is high among persons with opioid dependence and alcohol dependence. According to a recent review, it is common for patients to use both opioids and alcohol, and this is seen especially in cases where the patient also experiences chronic pain. Nevertheless, alcohol use is often omitted from research on opioids and chronic pain. The review concludes that there is a great need for more knowledge about co-use of alcohol and opioids in people with chronic pain.
The high prevalence of chronic pain in populations with opioid or alcohol dependence could be related to comorbid physical illness and injuries, which is prevalent among opioid dependent patients. It is also possible that use of opioids or alcohol can contribute to pain sensitivity and worsening of pain over time.
There have been few studies focusing on chronic pain and dependence on other substances than opioids or alcohol. The prevalence of chronic pain among people with, for example, amphetamine dependence or cannabis dependence has received little attention, although cannabinoids are also used as prescription painkillers.
A study of the general population in the United States found a link between chronic pain and marijuana use, but could not discern whether the pain or marijuana use came first. In a small study, two out of five people using marijuana or cocaine reported using the substances as pain relief. Amphetamine is also a highly relevant substance when it comes to pain, as amphetamines can be analgesic, and can enhance the analgesic effect of opioids.
Chronic pain is associated with poorer treatment outcomes, however there is little knowledge about how co-occurring chronic pain and substance dependence develops over time. More knowledge about the mechanisms behind co-occurring chronic pain and dependence can contribute to better treatment options for patients, both when it comes to the treatment of pain and dependence.
Chronic pain and PTSD
Chronic pain and pain intensity have a documented association with post-traumatic stress disorder (PTSD) in the general population, but have not been much explored among people with dependence. A small study has found a higher prevalence of chronic pain among people with co-occurring substance dependence and PTSD, but the study was not large enough (n = 133) to distinguish between dependence on different types of substances. One study (n = 150) found a higher prevalence of PTSD among methadone patients with chronic pain.
Unfortunately, PTSD is a diagnosis that has historically been considered difficult to treat among people with substance use disorder. Therefore PTSD is undertreated for these patients.
The link between chronic pain and PTSD is not fully understood. In some cases, the pain may be caused by a physical injury in connection with the event that caused the PTSD. Beyond these cases, some theories focus on shared vulnerability, or that chronic pain and PTSD reinforce each other through excessive reactions to or misinterpretation of stress or pain stimuli. Other theories focus on the biological aspects, such as dysregulation of the nervous system or dysregulation of opioid receptors.
It is also possible that the PTSD symptoms associated with overactivation may drive the association between PTSD and pain. This makes it relevant to explore any potential interaction effects of PTSD symptoms and the use of sedative and stimulating substances/medications on the experience of pain.
A better understanding of the links between chronic pain, PTSD and dependence can mean a lot for better treatment of patients with comorbid substance dependence, PTSD and pain disorders.
METHODS
Design. Cross-sectional survey study, with linkage to retrospective and prospective registry data. The NOR-APT study employs a rarely utilized research design where survey data containing the patients' self-reported experiences are combined with high quality, nearly complete, longitudinal registry data from the first and second line health care services and the prescription database, as well as sociodemographic registries.
Data from the first registration of the patient in the registries can be linked to self-reported data through personal identification numbers retained by all residents, providing a complete history of treatments and diagnoses.
It is a multicentre study, with data collected from over 20 substance use treatment centres in the catchment areas for Akershus University Hospital, Oslo University Hospital, Vestfold Hospital Trust and Telemark Hospital in Norway.
Participants. The goal is to recruit 1 500 patients entering any form of substance use treatment at the 20+ collaborating inpatient and outpatient clinics.
Staff at the treatment centres are instructed to ask all patients. At the time-points where 500 and 1 000 questionnaires have been completed, the investigators will assess the distribution of participants according to their primary substance use problem/the substance they are in treatment for. If the distribution is skewed in a manner that may not give enough data about some sub-groups of substance users, the investigators may encourage staff at the treatment centres to continue with more selective recruitment of the patient groups that are underrepresented. For instance, many patients are treated for opioid or alcohol dependence, so this group may be recruited faster and more easily, while patients with a primary dependence to cannabis or amphetamines may be fewer and could require more time and effort to reach a sufficiently large sample size.
Materials. The questionnaire was developed based on the research questions, previous literature, and in collaboration with the clinicians that see the patient groups in their day to day practice at Akershus University Hospital and Oslo University Hospital. The questionnaire was piloted on 10 patients with different substance use patterns, where patients were asked to comment on the experience of filling in the questionnaire, the length and clarity of the questions, and give any other comments or suggestions. Further adjustments to the layout and wording of certain questions were made based on the results of the piloting.
To make the data-collection process as uniform as possible, a questionnaire guide for staff was made, with a standard text for introducing and explaining the questionnaire to patients, and with a walk-through of the questions with additional explanations, definitions and problem-solving for common issues when filling out the different type of questions. In the guide, other topics related to collecting survey-data were also addressed, such as concerns related to missing responses for data validity and how to balance the preference for complete answers with ensuring that all questions were answered on a completely voluntary basis.
An instructional 15 minute video for staff was made, with an explanation of the background and purpose of the study, as a measure to increase understanding and motivation for recruiting patients to the study.
Registry data: The Norwegian registries consist of high-quality data on for instance treatment episodes, diagnoses, prescribed medications and socioeconomic variables, with nearly complete data for all individuals in Norway.
Procedure. Each treatment centre has a study coordinator responsible for ensuring all staff has access to questionnaires, guides and the instructional video. The coordinators task is to inform staff and distributed the study material. The coordinator will also report on progress, issues and concerns to the central study coordinators throughout the data collection period.
Staff at the treatment centres are instructed to invite all patients (except those affected by the exclusion criteria) to participate. Patients will be informed that participation is voluntary and that declining to participate will not affect the treatment they receive, about the purpose of the study and how the information they give will be handled. The number of patients that decline participation will be logged, and if the patients consent to disclosing the information, the gender, age and which substance they are in treatment for/their primary substance problem, will also be logged for patients that decline participation.
Patients that agree to participate will complete the consent form and the questionnaire. If they wish to withdraw from the study at a later time, they can contact the treatment centre or the research group.
For participants who consent to linkage of questionnaire data with longitudinal registry data, linkage to retrospective registry data will be performed about a year after collection of questionnaire data has been completed, and linkage to prospective registry data will be done 5-6 years after the collection of questionnaire data have been completed. Linkages are performed by the Norwegian Institute of Public Health and Statistics Norway, based on the patients explicit consent and unique personal identification number.
- Keywords
- Opioid, Alcohol, Amphetamine, Cannabis, Marijuana, Methadone, Buprenorphine, Opioid maintenance treatment, Chronic pain, Post-traumatic stress
- Medical subject headings
- Chronic Pain, Stress Disorders, Post-Traumatic, Substance-Related Disorders, Marijuana Abuse
What is being measured
The primary outcome is the main question the study is designed to answer.
Chronic pain (ICD-10)
Defined as having experienced pain with a duration of at least 3 months.
Measured: T1 (at enrollment in study)
European-Addiction Severity Index (EuropASI), Section E
- Types of substances used (life-time), age of first use, and frequency of use in the last 4 weeks.
- Intravenous use (life-time and last 4 weeks)
Modifications:
- We updated the list of substances to better match the relevant substances in use today: Alcohol to intoxication; OMT medications (methadone; subutex; suboxone); Other opioid painkillers (e.g. morphine, oxycodone, tramadol); Cannabis; Amphetamine/ Methamphetamine; Cocaine; Benzodiazepines; GHB; Hallucinogenics (e.g. LSD, mushrooms, mescaline); Anabolic steroids; Khat.
- Frequency of use in the last 4 weeks: the response categories "used not more than 2-3 times per month" and " used 1-3 times a week" were collapsed into one category "used a few times", leaving three categories: "Not used", "used a few times" and "every day/nearly every day".
Measured: T1 (at enrollment in study)
The Stressful Life-Events Screening Questionnaire (SLESQ)
The SLESQ assesses exposure to stressful life-events (yes/no) that could be potentially traumatizing. This version has been shortened and adapted in previous studies at the Norwegian Centre for Violence and Traumatic Stress Studies (NKVTS) for use in Norway and includes a list of 15 types of stressful events. This variable will be used to assess the prevalence of different types of stressful life-events. In addition the number of events can be summed to indicate the extent of exposure to stressful life-event, with a range from 0 events to 15.
Modifications:
- Two events have been added: Being directly involved in a natural disaster and having been repeatedly ridiculed, put down, ignored or told you were no good by someone outside the family.
- When several of the 15 types of events have occured, the participants' age at the time of the event is only recorded for the first event and the event that gives the participant the most symptoms now.
Measured: T1 (at enrollment in study)
The PTSD Checklist for DSM-5 - short version (PCL-5 short)
The short version of the PTSD Checklist for DSM-5 includes 4 items: 1 item for each symptom cluster for the diagnosis of PTSD according to the DSM-5.
Participants indicate how much each symptom has bothered them in the last month on a scale from 0 to 4 ("Not at all" to "Very much"). The sum score ranges from 0 to 16. A score above the cut score of 10 indicates risk for PTSD, and has previously been validated as a diagnostic indicator.
Measured: T1 (at enrollment in study)
Secondary outcomes (19)
Pain characteristics
Patients that report any pain in the last 4 weeks are asked:
- to indicate the location/s of the pain on a body map with 25 different pain locations (from the Norwegian Pain Association)
- to indicate any generalized pain in the skin, muscles, joints or skeleton/bones (selfmade checklist).
- the duration of their pain (less than 3 months; 3-12 months; 1-3 years; 4-6 years; 7-10 years; more than 10 years)
- the cause of their pain (illness; accident/injury; violence; surgery; other; unknown), their age at that time and whether they believe the cause was related to their substance use (selfmade questions, the list of causes collected from previous studies).
Measured: T1 (at enrollment in study)
The Brief Pain Inventory: Pain intensity
Pain intensity will be assess with 4 items addressing pain intensity right now; on average; the strongest in the last week; the weakest in the last week. Responses are given on an 11 point numeric rating scale from 0 "No pain" to 10 "The worst pain imaginable". These 4 items can be used independently or averaged.
Measured: T1 (at enrollment in study)
The Brief Pain Inventory: Pain interference
Pain interference on different life domains in the last week will be assessed with 7 items from the BPI: general activity, ability to walk, normal work/housework, mood, sleep, relationships to others, enjoyment of life
Responses are given on an 11 point numeric rating scale from 0 "Not influenced at all" to 10 "Completely influenced".
The 7 items can be averaged to give an overall interference score from 0 (low) to 10 (high), or they can be divided into affective interference (mood, sleep, relationships, enjoyment of life) and activity interference (walking, activity, work).
In addition, we include1 selfmade item in the same format, about interference on subjective quality of life: satisfaction with life.
Measured: T1 (at enrollment in study)
Other pain related questions (selfmade)
- Have you contacted a medical doctor for help with your pain? (Yes/no). If yes, age at the time (open ended question)
- Did you receive treatment for your pain? (yes/no) If yes, what type of treatment (open ended question).
- Is it difficult for you now to stop using substances/medications because of
- pain? (No/ A little/ Very)
- worrying about pain? (No/ A little/ Very)
- Are there substance/medications (including over the counter pain medications) that...
- ...help with your pain? (open ended question)
- ... make your pain worse? (open ended question)
- The first time you used opioids, was it to relieve pain? (Never used opioids/No/Yes/Don't know)
- Has pain ever influenced the type of medication received in OMT? (No/Yes/Don't know) If yes, which medication? (open ended), what was your age at the time? (open ended), Any comments? (open ended).
Measured: T1 (at enrollment in study)
Opioid maintenance treatment (OMT) history (selfmade)
- Have you ever been in OMT? (No/Methadone/Subutex/Buvidal/Suboxone/Other (specify)) Age at the time of the first prescription.
- Are you in OMT now? (No/Methadone/Subutex/Buvidal/Suboxone/Other (specify)) Age at the start of this prescription.
Measured: T1 (at enrollment in study)
Subjective quality of life (QOL-1)
- How satisfied are you with your life? The response is given on an 11-point numeric rating scale, from 0 "Not satisfied at all" to 10 "Very satisfied".
Measured: T1 (at enrollment in study)
Demographics
- Age
- Gender (Woman/man)
- Are you currently working/studying? (No/Yes (full or parttime) OR On sickleave/Retired/Disabled)
Measured: T1 (at enrollment in study)
Nicotine use
- Do you smoke cigarettes or a pipe? (Yes/No)
- Do you use snuff? (Yes/No)
Measured: T1 (at enrollment in study)
ICD-10/11 diagnostic codes
From the Norwegian Patient Registry (NPR) we wi receive all registered contacts/treatments with the secondary specialist health care services (for somatic diseases, mental health and substance dependence), including ICD codes and dates for treatment start and end.
Measured: Retrospective (back to 2008) and prospective (5 year follow-up from completion of the questionnaire)
Prescribed medications
From the Norwegian Prescription Database (NorPD) we will receive all registered medications with dates for when they were collected from the pharmacy.
Measured: Retrospective (back to 2004) and prospective (5 year follow-up from completion of the questionnaire)
Treatments in the primary health services
From the municipal health registry (KPR) we will receive codes for all treatments in the primary (municipal) health services, including emergency care, general practitioners and dentists.
Measured: Retrospective (back to 2016) and prospective (5 year follow-up from completion of the questionnaire)
Pain treatment
From the national quality registry for pain treatment (SmerteReg) we can receive additional details concerning pain treatment
Measured: Retrospective (back to 2013) and prospective (5 year follow-up from completion of the questionnaire)
Treatments of patients with severe physical trauma
From the national traumaregister (NTR) we can receive information on patients who have received treatments for severe physical trauma.
Measured: Retrospective (since establishment of database) and prospective (5 year follow-up from completion of the questionnaire)
Cancer diagnosis and treatments
From the Cancer registry we can receive additional information on cancer diagnosis and treatments.
Measured: Retrospective (since establishment of database) and prospective (5 year follow-up from completion of the questionnaire)
Time and cause of death
From the Cause of death registry we will receive the date and cause of death for patients who have died during the 5-year follow-up period.
Measured: Prospective (5 year follow-up from completion of the questionnaire)
Level of education
From the demographic database of Statistics Norway we will receive information on the highest level of completed education.
Measured: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Birthcountry and immigration status
From the demographic database of Statistics Norway we will receive information on birth country and 1st, 2nd and 3rd generation immigration status.
Measured: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Income and employment status
From the demographic database of Statistics Norway we will receive information of types of income and employment status, sick-leave and benefits.
Measured: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Living conditions
From the demographic database of Statistics Norway we will receive information on type of dwelling, number of persons in the household, moves between houses.
Measured: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2021
- Study start23 Mar 2021
- Primary completion2 Jun 2024
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (22)Papers the sponsor has linked to this study.
- Other trials for Chronic PainStudies of the same condition, open and under way.
- 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
- Observational
- Observational model
- Case only
- Time perspective
- Other
- Enrolment
- 1,650 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Akershus
- Sponsor type
- University, hospital or other
- Collaborators
- Oslo University Hospital, Norwegian Center for Violence and Traumatic Stress Studies, The Hospital of Vestfold, Sykehuset Telemark
- Responsible party
- Principal investigator, Ingeborg Skjarvo, University Hospital, Akershus
- Investigators
- Ingeborg Skjærvø, PhD, Principal investigator, Ingeborg Skjærvø
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04908410
- Sponsor's protocol ID
- 2020/173249(REK)
- Acronym
- NOR-APT
- Status last verified
- Dec 2024
- First submitted
- 18 May 2021
- Last updated
- 27 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Latif ZH, Skjaervo I, Solli KK, Tanum L. Chronic Pain Among Patients With an Opioid Use Disorder. Am J Addict. 2021 Jul;30(4):366-375. doi: 10.1111/ajad.13153. Epub 2021 Mar 19.
PubMed 33738870Rosenblum A, Joseph H, Fong C, Kipnis S, Cleland C, Portenoy RK. Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities. JAMA. 2003 May 14;289(18):2370-8. doi: 10.1001/jama.289.18.2370.
PubMed 12746360Boissoneault J, Lewis B, Nixon SJ. Characterizing chronic pain and alcohol use trajectory among treatment-seeking alcoholics. Alcohol. 2019 Mar;75:47-54. doi: 10.1016/j.alcohol.2018.05.009. Epub 2018 May 25.
PubMed 30359794Witkiewitz K, Vowles KE. Alcohol and Opioid Use, Co-Use, and Chronic Pain in the Context of the Opioid Epidemic: A Critical Review. Alcohol Clin Exp Res. 2018 Mar;42(3):478-488. doi: 10.1111/acer.13594. Epub 2018 Feb 6.
PubMed 29314075Larney S, Peacock A, Mathers BM, Hickman M, Degenhardt L. A systematic review of injecting-related injury and disease among people who inject drugs. Drug Alcohol Depend. 2017 Feb 1;171:39-49. doi: 10.1016/j.drugalcdep.2016.11.029. Epub 2016 Dec 8.
PubMed 28013096Pud D, Cohen D, Lawental E, Eisenberg E. Opioids and abnormal pain perception: New evidence from a study of chronic opioid addicts and healthy subjects. Drug Alcohol Depend. 2006 May 20;82(3):218-23. doi: 10.1016/j.drugalcdep.2005.09.007. Epub 2005 Oct 17.
PubMed 16229972Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states--maybe it is all in their head. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):141-54. doi: 10.1016/j.berh.2011.02.005.
PubMed 22094191Egli M, Koob GF, Edwards S. Alcohol dependence as a chronic pain disorder. Neurosci Biobehav Rev. 2012 Nov;36(10):2179-92. doi: 10.1016/j.neubiorev.2012.07.010. Epub 2012 Sep 11.
PubMed 22975446Apkarian AV, Neugebauer V, Koob G, Edwards S, Levine JD, Ferrari L, Egli M, Regunathan S. Neural mechanisms of pain and alcohol dependence. Pharmacol Biochem Behav. 2013 Nov;112:34-41. doi: 10.1016/j.pbb.2013.09.008. Epub 2013 Oct 2.
PubMed 24095683Hill KP. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA. 2015 Jun 23-30;313(24):2474-83. doi: 10.1001/jama.2015.6199.
PubMed 26103031Zvolensky MJ, Cougle JR, Bonn-Miller MO, Norberg MM, Johnson K, Kosiba J, Asmundson GJ. Chronic pain and marijuana use among a nationally representative sample of adults. Am J Addict. 2011 Nov-Dec;20(6):538-42. doi: 10.1111/j.1521-0391.2011.00176.x. Epub 2011 Oct 4.
PubMed 21999500Alford DP, German JS, Samet JH, Cheng DM, Lloyd-Travaglini CA, Saitz R. Primary Care Patients with Drug Use Report Chronic Pain and Self-Medicate with Alcohol and Other Drugs. J Gen Intern Med. 2016 May;31(5):486-91. doi: 10.1007/s11606-016-3586-5. Epub 2016 Jan 25.
PubMed 26809204Chen AL, Chen TJ, Waite RL, Reinking J, Tung HL, Rhoades P, Downs BW, Braverman E, Braverman D, Kerner M, Blum SH, DiNubile N, Smith D, Oscar-Berman M, Prihoda TJ, Floyd JB, O'Brien D, Liu HH, Blum K. Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions. Med Hypotheses. 2009 Jan;72(1):14-22. doi: 10.1016/j.mehy.2008.07.059. Epub 2008 Oct 31.
PubMed 18951726Larson MJ, Paasche-Orlow M, Cheng DM, Lloyd-Travaglini C, Saitz R, Samet JH. Persistent pain is associated with substance use after detoxification: a prospective cohort analysis. Addiction. 2007 May;102(5):752-60. doi: 10.1111/j.1360-0443.2007.01759.x.
PubMed 17506152Sharp TJ, Harvey AG. Chronic pain and posttraumatic stress disorder: mutual maintenance? Clin Psychol Rev. 2001 Aug;21(6):857-77. doi: 10.1016/s0272-7358(00)00071-4.
PubMed 11497210
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Norwegian Addiction, Pain and Trauma Study
- ClinicalTrials.gov ID
- NCT04908410
- Acronym / sponsor ID
- NOR-APT / 2020/173249(REK)
- Keywords
- Opioid, Alcohol, Amphetamine, Cannabis, Marijuana, Methadone, Buprenorphine, Opioid maintenance treatment
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,650 participants (actual)
- Lead sponsor
- University Hospital, AkershusUniversity, hospital or other
- Collaborators
- Oslo University Hospital, Norwegian Center for Violence and Traumatic Stress Studies, The Hospital of Vestfold, Sykehuset Telemark
- Study start
- 23 Mar 2021 (actual)
- Primary completion
- 2 Jun 2024 (actual)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 1 Jun 2021 (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.
In populations with substance use disorders (SUD), there is a high prevalence of chronic pain with various underlying causes. Chronic pain can complicate the treatment of SUD and lead to poorer treatment outcomes. There is a need for a better understanding of the connections and interactions between chronic pain and substance use and dependence.
Further, there is a high prevalence of chronic pain among patients with post-traumatic stress disorder (PTSD). As there is an overlap between populations with SUD and PTSD, taking potentially traumatizing life-experiences and post-traumatic stress symptoms into account can provide a better understanding of chronic pain in populations with SUD.
The Nor-APT study is a cross-sectional study, recruiting from outpatient and inpatient substance use treatment centres connected to four hospitals. Participants complete a questionnaire about substance/medication use, pain and how pain affect function, stressful life events and post-traumatic stress symptoms. Patients can consent to self-reported data being linked to retrospective and prospective longitudinal data from national demographic and health registries.
The purpose of the study is to contribute to a better understanding and treatment of chronic pain among people with substance use disorders (SUD), and to contribute to the understanding of co-occurring substance use, chronic pain and post-traumatic stress symptoms.
The over-arching research aims are to:
- Describe the prevalence and characteristics of pain for people in need of treatment for substance/medication use/dependence.
II. Describe how the pain affects physical and emotional functioning, and subjective quality of life.
III. Explore any connections between substance/medication use and pain, both what came first and any ways substance/medication use and pain affect each other.
IV. Explore the connection between chronic pain, potentially traumatizing life events and post-traumatic stress symptoms.
- Explore how treatments received and how treatment affects outcomes.
In addition, we will explore whether participants' experiences can be categorized into typical trajectories for how substance use, chronic pain and stressful life events occur and develop over the life span.
Detailed description
INTRODUCTION
Chronic pain and substance use
The prevalence of chronic pain is high among persons with opioid dependence and alcohol dependence. According to a recent review, it is common for patients to use both opioids and alcohol, and this is seen especially in cases where the patient also experiences chronic pain. Nevertheless, alcohol use is often omitted from research on opioids and chronic pain. The review concludes that there is a great need for more knowledge about co-use of alcohol and opioids in people with chronic pain.
The high prevalence of chronic pain in populations with opioid or alcohol dependence could be related to comorbid physical illness and injuries, which is prevalent among opioid dependent patients. It is also possible that use of opioids or alcohol can contribute to pain sensitivity and worsening of pain over time.
There have been few studies focusing on chronic pain and dependence on other substances than opioids or alcohol. The prevalence of chronic pain among people with, for example, amphetamine dependence or cannabis dependence has received little attention, although cannabinoids are also used as prescription painkillers.
A study of the general population in the United States found a link between chronic pain and marijuana use, but could not discern whether the pain or marijuana use came first. In a small study, two out of five people using marijuana or cocaine reported using the substances as pain relief. Amphetamine is also a highly relevant substance when it comes to pain, as amphetamines can be analgesic, and can enhance the analgesic effect of opioids.
Chronic pain is associated with poorer treatment outcomes, however there is little knowledge about how co-occurring chronic pain and substance dependence develops over time. More knowledge about the mechanisms behind co-occurring chronic pain and dependence can contribute to better treatment options for patients, both when it comes to the treatment of pain and dependence.
Chronic pain and PTSD
Chronic pain and pain intensity have a documented association with post-traumatic stress disorder (PTSD) in the general population, but have not been much explored among people with dependence. A small study has found a higher prevalence of chronic pain among people with co-occurring substance dependence and PTSD, but the study was not large enough (n = 133) to distinguish between dependence on different types of substances. One study (n = 150) found a higher prevalence of PTSD among methadone patients with chronic pain.
Unfortunately, PTSD is a diagnosis that has historically been considered difficult to treat among people with substance use disorder. Therefore PTSD is undertreated for these patients.
The link between chronic pain and PTSD is not fully understood. In some cases, the pain may be caused by a physical injury in connection with the event that caused the PTSD. Beyond these cases, some theories focus on shared vulnerability, or that chronic pain and PTSD reinforce each other through excessive reactions to or misinterpretation of stress or pain stimuli. Other theories focus on the biological aspects, such as dysregulation of the nervous system or dysregulation of opioid receptors.
It is also possible that the PTSD symptoms associated with overactivation may drive the association between PTSD and pain. This makes it relevant to explore any potential interaction effects of PTSD symptoms and the use of sedative and stimulating substances/medications on the experience of pain.
A better understanding of the links between chronic pain, PTSD and dependence can mean a lot for better treatment of patients with comorbid substance dependence, PTSD and pain disorders.
METHODS
Design. Cross-sectional survey study, with linkage to retrospective and prospective registry data. The NOR-APT study employs a rarely utilized research design where survey data containing the patients' self-reported experiences are combined with high quality, nearly complete, longitudinal registry data from the first and second line health care services and the prescription database, as well as sociodemographic registries.
Data from the first registration of the patient in the registries can be linked to self-reported data through personal identification numbers retained by all residents, providing a complete history of treatments and diagnoses.
It is a multicentre study, with data collected from over 20 substance use treatment centres in the catchment areas for Akershus University Hospital, Oslo University Hospital, Vestfold Hospital Trust and Telemark Hospital in Norway.
Participants. The goal is to recruit 1 500 patients entering any form of substance use treatment at the 20+ collaborating inpatient and outpatient clinics.
Staff at the treatment centres are instructed to ask all patients. At the time-points where 500 and 1 000 questionnaires have been completed, the investigators will assess the distribution of participants according to their primary substance use problem/the substance they are in treatment for. If the distribution is skewed in a manner that may not give enough data about some sub-groups of substance users, the investigators may encourage staff at the treatment centres to continue with more selective recruitment of the patient groups that are underrepresented. For instance, many patients are treated for opioid or alcohol dependence, so this group may be recruited faster and more easily, while patients with a primary dependence to cannabis or amphetamines may be fewer and could require more time and effort to reach a sufficiently large sample size.
Materials. The questionnaire was developed based on the research questions, previous literature, and in collaboration with the clinicians that see the patient groups in their day to day practice at Akershus University Hospital and Oslo University Hospital. The questionnaire was piloted on 10 patients with different substance use patterns, where patients were asked to comment on the experience of filling in the questionnaire, the length and clarity of the questions, and give any other comments or suggestions. Further adjustments to the layout and wording of certain questions were made based on the results of the piloting.
To make the data-collection process as uniform as possible, a questionnaire guide for staff was made, with a standard text for introducing and explaining the questionnaire to patients, and with a walk-through of the questions with additional explanations, definitions and problem-solving for common issues when filling out the different type of questions. In the guide, other topics related to collecting survey-data were also addressed, such as concerns related to missing responses for data validity and how to balance the preference for complete answers with ensuring that all questions were answered on a completely voluntary basis.
An instructional 15 minute video for staff was made, with an explanation of the background and purpose of the study, as a measure to increase understanding and motivation for recruiting patients to the study.
Registry data: The Norwegian registries consist of high-quality data on for instance treatment episodes, diagnoses, prescribed medications and socioeconomic variables, with nearly complete data for all individuals in Norway.
Procedure. Each treatment centre has a study coordinator responsible for ensuring all staff has access to questionnaires, guides and the instructional video. The coordinators task is to inform staff and distributed the study material. The coordinator will also report on progress, issues and concerns to the central study coordinators throughout the data collection period.
Staff at the treatment centres are instructed to invite all patients (except those affected by the exclusion criteria) to participate. Patients will be informed that participation is voluntary and that declining to participate will not affect the treatment they receive, about the purpose of the study and how the information they give will be handled. The number of patients that decline participation will be logged, and if the patients consent to disclosing the information, the gender, age and which substance they are in treatment for/their primary substance problem, will also be logged for patients that decline participation.
Patients that agree to participate will complete the consent form and the questionnaire. If they wish to withdraw from the study at a later time, they can contact the treatment centre or the research group.
For participants who consent to linkage of questionnaire data with longitudinal registry data, linkage to retrospective registry data will be performed about a year after collection of questionnaire data has been completed, and linkage to prospective registry data will be done 5-6 years after the collection of questionnaire data have been completed. Linkages are performed by the Norwegian Institute of Public Health and Statistics Norway, based on the patients explicit consent and unique personal identification number.
Study design
- Observational model
- Case only
- Time perspective
- Other
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients (ages 18 years - unlimited) in treatment for substance use disorders at outpatient and inpatient treatment centers connected to Akerhus University Hospital or Oslo University Hospital, Norway.
Key inclusion criteria (1 listed)
- Patient in substance use treatment at a treatment centre under Akershus University Hospital, Oslo University Hospital, Vestfold Hospital or Telemark Hospital.
Key exclusion criteria (5 listed)
- Staff considers the patient to be unable to give informed consent/valid responses on the questionnaire OR staff considers participation to be too stressful/burdensome to the patient. Staff are asked to take the following into consideration when making their assessment:
- Acute withdrawal
- Acute intoxication
- Serious mental health concerns
- Serious physical health concerns
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Chronic pain (ICD-10)
Time frame: T1 (at enrollment in study)
Defined as having experienced pain with a duration of at least 3 months.
European-Addiction Severity Index (EuropASI), Section E
Time frame: T1 (at enrollment in study)
* Types of substances used (life-time), age of first use, and frequency of use in the last 4 weeks. * Intravenous use (life-time and last 4 weeks) Modifications: 1. We updated the list of substances to better match the relevant substances in use today: Alcohol to intoxication; OMT medications (methadone; subutex; suboxone); Other opioid painkillers (e.g. morphine, oxycodone, tramadol); Cannabis; Amphetamine/ Methamphetamine; Cocaine; Benzodiazepines; GHB; Hallucinogenics (e.g. LSD, mushrooms, mescaline); Anabolic steroids; Khat. 2. Frequency of use in the last 4 weeks: the response categories "used not more than 2-3 times per month" and " used 1-3 times a week" were collapsed into one category "used a few times", leaving three categories: "Not used", "used a few times" and "every day/nearly every day".
The Stressful Life-Events Screening Questionnaire (SLESQ)
Time frame: T1 (at enrollment in study)
The SLESQ assesses exposure to stressful life-events (yes/no) that could be potentially traumatizing. This version has been shortened and adapted in previous studies at the Norwegian Centre for Violence and Traumatic Stress Studies (NKVTS) for use in Norway and includes a list of 15 types of stressful events. This variable will be used to assess the prevalence of different types of stressful life-events. In addition the number of events can be summed to indicate the extent of exposure to stressful life-event, with a range from 0 events to 15. Modifications: 1. Two events have been added: Being directly involved in a natural disaster and having been repeatedly ridiculed, put down, ignored or told you were no good by someone outside the family. 2. When several of the 15 types of events have occured, the participants' age at the time of the event is only recorded for the first event and the event that gives the participant the most symptoms now.
The PTSD Checklist for DSM-5 - short version (PCL-5 short)
Time frame: T1 (at enrollment in study)
The short version of the PTSD Checklist for DSM-5 includes 4 items: 1 item for each symptom cluster for the diagnosis of PTSD according to the DSM-5. Participants indicate how much each symptom has bothered them in the last month on a scale from 0 to 4 ("Not at all" to "Very much"). The sum score ranges from 0 to 16. A score above the cut score of 10 indicates risk for PTSD, and has previously been validated as a diagnostic indicator.
19 secondary outcomes
Pain characteristics
Time frame: T1 (at enrollment in study)
The Brief Pain Inventory: Pain intensity
Time frame: T1 (at enrollment in study)
The Brief Pain Inventory: Pain interference
Time frame: T1 (at enrollment in study)
Other pain related questions (selfmade)
Time frame: T1 (at enrollment in study)
Opioid maintenance treatment (OMT) history (selfmade)
Time frame: T1 (at enrollment in study)
Subjective quality of life (QOL-1)
Time frame: T1 (at enrollment in study)
Demographics
Time frame: T1 (at enrollment in study)
Nicotine use
Time frame: T1 (at enrollment in study)
ICD-10/11 diagnostic codes
Time frame: Retrospective (back to 2008) and prospective (5 year follow-up from completion of the questionnaire)
Prescribed medications
Time frame: Retrospective (back to 2004) and prospective (5 year follow-up from completion of the questionnaire)
Treatments in the primary health services
Time frame: Retrospective (back to 2016) and prospective (5 year follow-up from completion of the questionnaire)
Pain treatment
Time frame: Retrospective (back to 2013) and prospective (5 year follow-up from completion of the questionnaire)
Treatments of patients with severe physical trauma
Time frame: Retrospective (since establishment of database) and prospective (5 year follow-up from completion of the questionnaire)
Cancer diagnosis and treatments
Time frame: Retrospective (since establishment of database) and prospective (5 year follow-up from completion of the questionnaire)
Time and cause of death
Time frame: Prospective (5 year follow-up from completion of the questionnaire)
Level of education
Time frame: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Birthcountry and immigration status
Time frame: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Income and employment status
Time frame: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Living conditions
Time frame: Retrospective (back to 1960s) and prospective (5 year follow-up from completion of the questionnaire)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2024.
- Background: PubMed 33738870Latif ZH, Skjaervo I, Solli KK, Tanum L. Chronic Pain Among Patients With an Opioid Use Disorder. Am J Addict. 2021 Jul;30(4):366-375. doi: 10.1111/ajad.13153. Epub 2021 Mar 19.
- Background: PubMed 12746360Rosenblum A, Joseph H, Fong C, Kipnis S, Cleland C, Portenoy RK. Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities. JAMA. 2003 May 14;289(18):2370-8. doi: 10.1001/jama.289.18.2370.
- Background: PubMed 30359794Boissoneault J, Lewis B, Nixon SJ. Characterizing chronic pain and alcohol use trajectory among treatment-seeking alcoholics. Alcohol. 2019 Mar;75:47-54. doi: 10.1016/j.alcohol.2018.05.009. Epub 2018 May 25.
- Background: PubMed 29314075Witkiewitz K, Vowles KE. Alcohol and Opioid Use, Co-Use, and Chronic Pain in the Context of the Opioid Epidemic: A Critical Review. Alcohol Clin Exp Res. 2018 Mar;42(3):478-488. doi: 10.1111/acer.13594. Epub 2018 Feb 6.
- Background: PubMed 28013096Larney S, Peacock A, Mathers BM, Hickman M, Degenhardt L. A systematic review of injecting-related injury and disease among people who inject drugs. Drug Alcohol Depend. 2017 Feb 1;171:39-49. doi: 10.1016/j.drugalcdep.2016.11.029. Epub 2016 Dec 8.
- Background: PubMed 16229972Pud D, Cohen D, Lawental E, Eisenberg E. Opioids and abnormal pain perception: New evidence from a study of chronic opioid addicts and healthy subjects. Drug Alcohol Depend. 2006 May 20;82(3):218-23. doi: 10.1016/j.drugalcdep.2005.09.007. Epub 2005 Oct 17.
- Background: PubMed 22094191Phillips K, Clauw DJ. Central pain mechanisms in chronic pain states--maybe it is all in their head. Best Pract Res Clin Rheumatol. 2011 Apr;25(2):141-54. doi: 10.1016/j.berh.2011.02.005.
- Background: PubMed 22975446Egli M, Koob GF, Edwards S. Alcohol dependence as a chronic pain disorder. Neurosci Biobehav Rev. 2012 Nov;36(10):2179-92. doi: 10.1016/j.neubiorev.2012.07.010. Epub 2012 Sep 11.
- Background: PubMed 24095683Apkarian AV, Neugebauer V, Koob G, Edwards S, Levine JD, Ferrari L, Egli M, Regunathan S. Neural mechanisms of pain and alcohol dependence. Pharmacol Biochem Behav. 2013 Nov;112:34-41. doi: 10.1016/j.pbb.2013.09.008. Epub 2013 Oct 2.
- Background: PubMed 26103031Hill KP. Medical Marijuana for Treatment of Chronic Pain and Other Medical and Psychiatric Problems: A Clinical Review. JAMA. 2015 Jun 23-30;313(24):2474-83. doi: 10.1001/jama.2015.6199.
- Background: PubMed 21999500Zvolensky MJ, Cougle JR, Bonn-Miller MO, Norberg MM, Johnson K, Kosiba J, Asmundson GJ. Chronic pain and marijuana use among a nationally representative sample of adults. Am J Addict. 2011 Nov-Dec;20(6):538-42. doi: 10.1111/j.1521-0391.2011.00176.x. Epub 2011 Oct 4.
- Background: PubMed 26809204Alford DP, German JS, Samet JH, Cheng DM, Lloyd-Travaglini CA, Saitz R. Primary Care Patients with Drug Use Report Chronic Pain and Self-Medicate with Alcohol and Other Drugs. J Gen Intern Med. 2016 May;31(5):486-91. doi: 10.1007/s11606-016-3586-5. Epub 2016 Jan 25.
- Individual participant dataSharing planned: Undecided
Related trials for Chronic Pain
Recruiting
Empowered Relief® for Cancer Survivors With Chronic Pain
Chronic Pain Due to Cancer, Pain Catastrophizing
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Effect of Lumbar Stabilization Exercises With and Without YTWL (Scapular Stabilization Exercises) on Reducing Chronic Low Back Pain and Related Disability. A Randomized Clinical Trial,
Chronic Non Specific Mechanical Low Back Pain
Not yet recruiting
Comparing Non-Medicine Strategies for Improving Low Back Pain
Chronic Low-back Pain (cLBP), High-Impact Chronic Pain (HICP)
Not yet recruiting
Effect of Pectoral Nerve Block (PECS) Using Magnesium Sulfate Added to Dexamethasone on Quality of Recovery and Chronic Post-Mastectomy Pain
Breast Cancer, Postoperative Pain
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.
Ingeborg Skjærvø, PhD principal investigator
Ingeborg Skjærvø
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Pain and Post-traumatic Stress Disorder, run by University Hospital, Akershus at 4 sites in Norway.
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 1 inclusion and 5 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: under way, not looking for participants, as of the sponsor's last update on 27 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
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?
Chronic pain (ICD-10) (time frame: T1 (at enrollment in study)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04908410, which also lists 22 linked publications.
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 27 Dec 2024.