The Norwegian Addiction, Pain and Trauma Study

Chronic Pain Clinical Trial

— NOR-APT  

Official title:

The Norwegian Addiction, Pain and Trauma Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04908410
• Other study ID #: 2020/173249(REK)
• Status: Recruiting
• Start date: March 23, 2021
• Est. completion date: February 1, 2024

Study information

• Verified date: March 2023
• Source: University Hospital, Akershus
• Contact: Ingeborg Skjærvø, PhD
• Phone: 004741453842
• Email: ingeborg.skjarvo[@]nkvts.no
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

THIS STUDY DOES NOT OFFER ANY FORM OF TREATMENT FOR PTSD, PAIN OR SUBSTANCE DEPENDENCE. 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, where the goal is to recruit 1 500 patients from outpatient and inpatient substance use treatment centres connected to Akershus University Hospital and Oslo University Hospital in Norway. Participants are invited to complete a questionnaire about substance/medication use, pain and how pain affect function, stressful life events and post-traumatic stress symptoms. The questionnaire has been developed in collaboration with clinicians at the various substance dependence treatment units and the Norwegian Centre for Violence and Traumatic Stress Studies (NKVTS). The purpose of the Nor-APT 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 four over-arching research aims are to: I. 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. In addition, the investigators 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.

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. Multicentre, with data collected from 15 substance use treatment centres in the catchment areas for Akershus University Hospital and Oslo University Hospital in Norway. Participants. The goal is to recruit 1 500 patients entering any form of substance use treatment at the 15 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. 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1500
• Est. completion date: February 1, 2024
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient in substance use treatment at a treatment centre under Akershus University Hospital or Oslo University Hospital. Exclusion Criteria: 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

Related Conditions & MeSH terms

• Chronic Pain
• Disease
• Post-traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic
• Substance Use Disorders
• Substance-Related Disorders

Locations

Country	Name	City	State
Norway	Akershus University Hospital	Lørenskog
Norway	Oslo University Hospital	Oslo
Norway	Telemark Hospital	Skien
Norway	The Hospital in Vestfold	Tønsberg

Sponsors (5)

Lead Sponsor	Collaborator
University Hospital, Akershus	Norwegian Center for Violence and Traumatic Stress Studies, Oslo University Hospital, Sykehuset Telemark, The Hospital of Vestfold

Country where clinical trial is conducted

Norway, 

References & Publications (21)

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Apkarian 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. — View Citation

Barry DT, Beitel M, Cutter CJ, Garnet B, Joshi D, Rosenblum A, Schottenfeld RS. Exploring relations among traumatic, posttraumatic, and physical pain experiences in methadone-maintained patients. J Pain. 2011 Jan;12(1):22-8. doi: 10.1016/j.jpain.2010.04.006. Epub 2010 Jun 20. — View Citation

Boissoneault 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. — View Citation

Chen 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. — View Citation

Egli 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. — View Citation

Fishbain DA, Pulikal A, Lewis JE, Gao J. Chronic Pain Types Differ in Their Reported Prevalence of Post -Traumatic Stress Disorder (PTSD) and There Is Consistent Evidence That Chronic Pain Is Associated with PTSD: An Evidence-Based Structured Systematic Review. Pain Med. 2017 Apr 1;18(4):711-735. doi: 10.1093/pm/pnw065. — View Citation

Flanagan JC, Korte KJ, Killeen TK, Back SE. Concurrent Treatment of Substance Use and PTSD. Curr Psychiatry Rep. 2016 Aug;18(8):70. doi: 10.1007/s11920-016-0709-y. — View Citation

Hill 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. Erratum In: JAMA. 2016 Sep 6;316(9):995. — View Citation

Larney 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. — View Citation

Larson 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. — View Citation

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. — View Citation

Moeller-Bertram T, Keltner J, Strigo IA. Pain and post traumatic stress disorder - review of clinical and experimental evidence. Neuropharmacology. 2012 Feb;62(2):586-97. doi: 10.1016/j.neuropharm.2011.04.028. Epub 2011 May 10. — View Citation

Ouimette P, Goodwin E, Brown PJ. Health and well being of substance use disorder patients with and without posttraumatic stress disorder. Addict Behav. 2006 Aug;31(8):1415-23. doi: 10.1016/j.addbeh.2005.11.010. Epub 2005 Dec 27. — View Citation

Pacella ML, Girard JM, Wright AGC, Suffoletto B, Callaway CW. The Association Between Daily Posttraumatic Stress Symptoms and Pain Over the First 14 Days After Injury: An Experience Sampling Study. Acad Emerg Med. 2018 Aug;25(8):844-855. doi: 10.1111/acem.13406. — View Citation

Phillips 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. — View Citation

Pud 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. — View Citation

Rosenblum 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. — View Citation

Sharp 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. — View Citation

Witkiewitz 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. — View Citation

Zvolensky 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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Chronic pain (ICD-10)	Defined as having experienced pain with a duration of at least 3 months.	T1 (at enrollment in study)
Primary	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".	T1 (at enrollment in study)
Primary	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.	T1 (at enrollment in study)
Primary	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.	T1 (at enrollment in study)
Secondary	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).	T1 (at enrollment in study)
Secondary	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.	T1 (at enrollment in study)
Secondary	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.	T1 (at enrollment in study)
Secondary	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).	T1 (at enrollment in study)
Secondary	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.	T1 (at enrollment in study)
Secondary	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".	T1 (at enrollment in study)
Secondary	Demographics	Age; Gender (Woman/man); Are you currently working/studying? (No/Yes (full or parttime) OR On sickleave/Retired/Disabled)	T1 (at enrollment in study)
Secondary	Nicotine use	Do you smoke cigarettes or a pipe? (Yes/No); Do you use snuff? (Yes/No)	T1 (at enrollment in study)