Chronic Pain in Patients in Hemodialysis

Chronic Pain Clinical Trial

— DolERC  

Official title:

Chronic Pain in Patients With Chronic Kidney Disease in Hemodialysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06311240
• Other study ID #: 02-24-108-003
• Status: Recruiting
• Start date: May 2, 2024
• Est. completion date: September 2024

Study information

• Verified date: June 2024
• Source: Cardenal Herrera University
• Contact: Eva F Segura-Ortí, PhD
• Phone: 00034961369000
• Email: ESEGURA[@]UCHCEU.ES
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Pain is one of the most common symptoms among patients with End Stage Renal Disease (ESRD), and often goes unrecognized or inadequately managed in hemodialysis patients. More than 50% of patients undergoing hemodialysis suffer from pain, with 75% of them being treated ineffectively due to healthcare professionals' lack of awareness of this symptom. Therefore, pain management in this population is a complex and challenging task for healthcare providers. The most prevalent pain syndromes in hemodialysis patients include musculoskeletal disorders, metabolic neuropathies, in addition to typical intradialytic pain.

The aim of this study is to assess the presence and characteristics of chronic pain in patients with ESRD undergoing hemodialysis to determine whether it is relevant to include the management of chronic pain in the holistic treatment (physical activity, nutrition, and psychological support) already being implemented in various studies for these patients.

Description:

Chronic Kidney Disease (CKD) has an estimated prevalence ranging from 13.4% to 10.6% across stages 1 to 5. These data indicate that CKD is recognized as a major global health issue, with high healthcare costs. Its incidence increases with age, with individuals over 65 years old comprising 40% of CKD patients. Gender differences exist, with males being more affected, although females exhibit greater frailty and severity. This population often presents high comorbidity with other conditions such as diabetes, hypertension, and cardiovascular diseases, along with malnutrition, sedentary lifestyles, poor health-related quality of life, low functional capacity, frailty, high levels of dependency, and, recently evidenced, pain. All of these factors are associated with increased mortality risk, exceeding 15% annually. Cardiovascular disease is the leading cause of death in patients with advanced CKD and a significant risk factor for peripheral arterial disease and lower limb amputation.

Chronic pain imposes a significant personal and economic burden, affecting over 30% of people worldwide. Unlike acute pain, which serves a protective function, chronic pain may be better considered as a disease itself, with both physical and psychological implications. There has been a growing acceptance of the biopsychosocial model in addressing patients with chronic pain, understanding pain as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage," according to the International Association for the Study of Pain (IASP). This perspective considers pain not only as a purely nociceptive experience but also as a personal experience involving both biological and emotional/psychological components.

Pain is one of the most common symptoms among patients with end-stage CKD, often going unrecognized or inadequately managed. Barriers to proper pain management include limited awareness of the problem, inadequate medical education, and common misconceptions about the inevitability of pain in older adults and HD patients. More than 50% of hemodialysis patients suffer from pain, with 75% of them receiving ineffective treatment due to healthcare professionals' lack of awareness of this symptom. Therefore, pain management in this population is a complex and challenging task. The most prevalent pain syndromes in hemodialysis patients include musculoskeletal disorders, metabolic neuropathies, and typical intradialytic puncture pain.

Patients with chronic pain from musculoskeletal disorders have been shown to exhibit high levels of catastrophizing, fear of movement, anxiety, depression, sleep disturbances, and elevated salivary cortisol levels due to the stress caused by chronic pain and the prevalence of musculoskeletal disorders as potential causes of pain in CKD patients.

Hormonal alterations at the hypothalamic-pituitary axis (HPA) level are frequently observed with worsening renal function. Traditionally, these alterations have been understood as a consequence of renal insufficiency. However, recent evidence suggests the involvement of such hormonal disorders in the genesis of CKD. The HPA axis controls stress responses through a negative feedback mechanism. If chronic pain is considered a stressor, a reciprocal response is triggered, with increased pain activating physiological mechanisms responding to stress, such as elevated cortisol, thereby increasing perceived pain. Chronic pain induces a chronic increase in cortisol and other central mediators of the HPA axis. Cortisol is one of the physiological indices used to quantify stress, with salivary cortisol levels reflecting HPA axis activity and quantifiable non-invasively through saliva samples using ELISA methods. Currently, physiological stress assessment is easily performed by measuring cortisol levels in saliva samples.

There is a gap in the literature regarding this topic as it has not been studied whether patients with advanced-stage CKD undergoing hemodialysis present the same characteristics of chronic pain as other pathologies, such as musculoskeletal disorders.

Methodology Study Type: A cross-sectional observational study will be conducted. Since no previous studies exist, a study with n: 20 will be conducted, and based on this data, the sample size calculation will be performed. Randomization and blinding will not be performed, and no intervention is planned.

Variables

The following measurement variables will be used in this study:

Biomarkers:

• Salivary Cortisol: Physiological stress assessment will be performed simply by measuring cortisol levels in a saliva sample and subsequently analyzed using the ELISA method.

The following questionnaires will be used to measure health condition variables:

• Sleep Quality: The validated Spanish version of the Pittsburgh Sleep Quality Index will be used.

• Stress: The validated Spanish version of the Perceived Stress Questionnaire will be used.

• Disease Self-Management: The self-efficacy questionnaire will be used.

The following questionnaire and physical variable measurement will be used to measure variables related to chronic pain:

• Chronic Pain Severity Scale: The validated Spanish version of the Chronic Pain Severity Scale will be used.

• Pressure Pain Thresholds (PPT): This variable is used to assess if the patient presents symptoms compatible with central sensitization. Pressure will be applied with an algometer at two bilateral points, the second rib and knee. Each measured subject will be instructed to say 'stop' when the pressure sensation becomes the first sensation of pain. Each measurement will be repeated three times with 10 seconds of rest between them.

The following questionnaire will be used to measure headache-related variables:

• HIT-6: The validated Spanish version of the Headache Impact Test-6 questionnaire will be used.

The following questionnaires will be used to measure behavioral variables:

• Catastrophizing: The validated Spanish version of the Pain Catastrophizing Scale will be used.

• Anxiety and Depression: The validated Spanish version of the Hospital Anxiety and Depression Scale (HADS) will be used.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: September 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients with End-Stage Renal Disease (ESRD)

• Have been on hemodialysis treatment for at least 3 months and are medically stable.

• Able to walk a few steps, even if they require walking aids such as canes or walkers.

Exclusion Criteria:

• Myocardial infarction in the past 6 weeks.

• Unstable angina during exercise or at rest.

• Amputation of lower limbs above the knee without prosthetics.

• Cerebrovascular disease such as stroke or transient ischemic attacks in the last 6 months or with significant sequelae affecting lower limb mobility.

• Musculoskeletal or respiratory disorders that worsen with exercise.

• Inability to perform study tests/questionnaires.

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Chronic Pain
• Kidney Diseases
• Renal Insufficiency, Chronic

Locations

Country	Name	City	State
Spain	Universidad Cardenal Herrera-CEU, CEU Universities	Alfara del Patriarca	Valencia
Spain	Consorci Sanitari de Terrassa	Terrassa	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Cardenal Herrera University	Consorci Sanitari de Terrassa

Country where clinical trial is conducted

Spain, 

References & Publications (12)

Arregger AL, Cardoso EM, Tumilasci O, Contreras LN. Diagnostic value of salivary cortisol in end stage renal disease. Steroids. 2008 Jan;73(1):77-82. doi: 10.1016/j.steroids.2007.09.001. Epub 2007 Sep 11. — View Citation

Cohen SP, Vase L, Hooten WM. Chronic pain: an update on burden, best practices, and new advances. Lancet. 2021 May 29;397(10289):2082-2097. doi: 10.1016/S0140-6736(21)00393-7. — View Citation

Coluzzi F. Assessing and Treating Chronic Pain in Patients with End-Stage Renal Disease. Drugs. 2018 Sep;78(14):1459-1479. doi: 10.1007/s40265-018-0980-9. — View Citation

Costa YM, Porporatti AL, Stuginski-Barbosa J, Bonjardim LR, Speciali JG, Conti PC. Headache attributed to masticatory myofascial pain: impact on facial pain and pressure pain threshold. J Oral Rehabil. 2016 Mar;43(3):161-8. doi: 10.1111/joor.12357. Epub 2015 Oct 6. — View Citation

Fujiwara A, Ida M, Watanabe K, Kawanishi H, Kimoto K, Yoshimura K, Shinohara K, Kawaguchi M. Prevalence and associated factors of disability in patients with chronic pain: An observational study. Medicine (Baltimore). 2021 Oct 8;100(40):e27482. doi: 10.1097/MD.0000000000027482. — View Citation

Hill NR, Fatoba ST, Oke JL, Hirst JA, O'Callaghan CA, Lasserson DS, Hobbs FD. Global Prevalence of Chronic Kidney Disease - A Systematic Review and Meta-Analysis. PLoS One. 2016 Jul 6;11(7):e0158765. doi: 10.1371/journal.pone.0158765. eCollection 2016. — View Citation

Hylands-White N, Duarte RV, Raphael JH. An overview of treatment approaches for chronic pain management. Rheumatol Int. 2017 Jan;37(1):29-42. doi: 10.1007/s00296-016-3481-8. Epub 2016 Apr 23. — View Citation

Luque-Suarez A, Martinez-Calderon J, Falla D. Role of kinesiophobia on pain, disability and quality of life in people suffering from chronic musculoskeletal pain: a systematic review. Br J Sports Med. 2019 May;53(9):554-559. doi: 10.1136/bjsports-2017-098673. Epub 2018 Apr 17. — View Citation

Meuwese CL, Carrero JJ. Chronic kidney disease and hypothalamic-pituitary axis dysfunction: the chicken or the egg? Arch Med Res. 2013 Nov;44(8):591-600. doi: 10.1016/j.arcmed.2013.10.009. Epub 2013 Nov 8. — View Citation

Raina R, Krishnappa V, Gupta M. Management of pain in end-stage renal disease patients: Short review. Hemodial Int. 2018 Jul;22(3):290-296. doi: 10.1111/hdi.12622. Epub 2017 Dec 11. — View Citation

Reyes del Paso GA, Perales Montilla CM. Haemodialysis course is associated to changes in pain threshold and in the relations between arterial pressure and pain. Nefrologia. 2011;31(6):738-42. doi: 10.3265/Nefrologia.pre2011.Oct.10902. English, Spanish. — View Citation

Sole E, Racine M, Tome-Pires C, Galan S, Jensen MP, Miro J. Social Factors, Disability, and Depressive Symptoms in Adults With Chronic Pain. Clin J Pain. 2020 May;36(5):371-378. doi: 10.1097/AJP.0000000000000815. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Stress level assessed by the salivary cortisol test	Higher stress present higher cortisol levels	Baseline
Primary	Stress level assessed by the perceived stress scale (PSS)	The minimal score is 0. The maximum PSS score is 56. The higher score obtained, the higher stress level	Baseline
Secondary	Self- efficacy assessed by questionnaire	The minimal score is 0. The maximun Self-efficacy score is 40. The lower score obtained , the lower self-efficacy	Baseline
Secondary	Quality of sleep assessed by Pittsburgh Sleep Quality Index	The minimal score is 0. The maximun quality index score is 21. The higher score obtained, the lower quality of sleep	Baseline
Secondary	The impact of headaches on life assessed by Headache Impact Test-6	The minimal score is 0. The maximun Headache Impact Test-6 score is 79. The higher score obtained, the higher impact of headaches on life	Baseline
Secondary	Anxiety and depression assessed by Hospital anxiety and depression scale (HADS)	The minimal score is 0. The cutoff point for the two subscales, anxiety and depression, is 8 and < 10. The higher score obtained, The higher impact of anxiety and depression levels on life.	Baseline
Secondary	Aspects of catastrophic cognitions about pain-rumination, magnification, and helplessness assessed by The Pain Catastrophizing Scale (PCS)	The minimal score is 0. The maximun The Pain Catastrophizing Scale score is 52. The higher score obtained, the higher impact of pain rumination, magnification and helplessness on life related to pain.	Baseline
Secondary	Chronic pain assessed by Chronic Pain Grade Questionnaire	The minimal score is 0. The maximun Chronic Pain Grade Questionnaire score is 70. The higher score obtained, the higher impact of chronic pain on life	Baseline