Pain, Sexual Dysfunction, and Depression in Hemodialysis Patients (SMILE)

• ClinicalTrials.gov Identifier: NCT00692419
• Recruitment Status: Completed
• First Posted: June 6, 2008
• Results First Posted: November 19, 2014
• Last Update Posted: April 27, 2015
• Sponsor: US Department of Veterans Affairs
• Collaborators: Dialysis Clinic, Inc.; Liberty Dialysis, LLC; DaVita Dialysis
• Information provided by (Responsible Party): VA Office of Research and Development ( US Department of Veterans Affairs )

Tracking Information

• First Submitted Date: June 4, 2008
• First Posted Date: June 6, 2008
• Results First Submitted Date: October 30, 2014
• Results First Posted Date: November 19, 2014
• Last Update Posted Date: April 27, 2015
• Study Start Date: November 2008
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 17, 2014)

Change in Pain, Sexual Dysfunction, and Depression Symptoms [ Time Frame: 12 months ]

The primary outcome of this study is the change in symptom scores during the intervention phase of the study

• Original Primary Outcome Measures (submitted: June 4, 2008): reduction in pain, sexual dysfunction, and depression symptoms [ Time Frame: 12 months ]
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pain, Sexual Dysfunction, and Depression in Hemodialysis Patients
• Official Title: Pain, Sexual Dysfunction and Depression in Hemodialysis Patients
• Brief Summary: This study is seeking to identify the most effective strategy to manage pain, sexual dysfunction, and depression in patients receiving chronic hemodialysis therapy.

Detailed Description

OBJECTIVES:

There are currently over 500,000 individuals with end-stage renal disease (ESRD) in the United States, and more than 100,000 new patients develop this condition annually. Recent estimates suggest that more than 35,000 veterans currently receive chronic hemodialysis. Although life-sustaining, hemodialysis is associated with substantial morbidity and mortality. Numerous studies have sought to identify interventions that reduce the mortality of patients dependent on hemodialysis, yet recent clinical trials of dialysis dose, dialysis membrane, and lipid lowering therapy have failed to demonstrate survival benefits. With the recognition that providers have limited means beyond renal transplantation to prolong the lives of patients on hemodialysis, investigators are beginning to refocus their research efforts on identifying interventions to improve patients' quality of life, which is substantially impaired in this population. Several major factors that contribute to poor quality of life have been identified, including the large burden of physical and emotional symptoms in this patient population.

Of the many symptoms that affect patients on hemodialysis, pain, sexual dysfunction, and depression are among the most prevalent, severe, and highly correlated with impaired quality of life. These observations are particularly noteworthy with recent data documenting the safety and efficacy of pharmacologic therapy for these symptoms. Nonetheless, preliminary studies suggest that even when severe, these symptoms are untreated or under-treated in patients on hemodialysis. The reasons for the sub-optimal treatment have not been clearly elucidated, but the investigators research demonstrated that renal providers are largely unaware of the presence and severity of pain, sexual dysfunction, and depression in their hemodialysis patients. Although increasing provider awareness of these symptoms would seem to be important for the provision of therapy, it is not clear that simply informing clinicians would be sufficient to improve treatment.

The broad objective of this 3-year project is to determine the most effective strategy for the management of pain, sexual dysfunction, and depression in patients on chronic hemodialysis. The investigators postulate that merely informing renal providers of patients' pain, sexual dysfunction, and depression and providing them with evidence-based treatment algorithms will not significantly improve the management of these symptoms. Rather, optimal symptom management will require assessment and treatment of these symptoms by a dedicated renal symptom management nurse. In a randomized clinical trial of not more than 350 patients receiving hemodialysis at 9 dialysis units, the investigators will compare two symptom management strategies: (a) providing feedback on patients' symptoms to renal providers along with evidence-based algorithms for their treatment and; (b) using a renal symptom management nurse to identify and facilitate treatment of these symptoms. This study involves the nurse and the research assistant bringing treatment plans and algorithms to the attention of the renal providers and does not involve any treatment by the research assistant and nurse themselves. By determining the most effective approach to the management of overall pain, sexual dysfunction, and depression, the investigators hope to introduce a patient-centered management approach to improve the quality of life of patients receiving chronic hemodialysis.

METHODS: Overview of Study Design The investigators have proposed a randomized, clinical trial to compare two strategies for the treatment of pain, sexual dysfunction, and depression in patients on chronic hemodialysis. The investigators have recruited 315 patients from nine local VA and non-VA dialysis units.

After enrollment, baseline data was collected from 289 patients, and an observation period of at least 2 months but not longer than 12 months ensued. Pain, sexual dysfunction, and depression were assessed monthly during this observation period, which allowed us to establish the stability of symptoms in study patients and obtain a valid estimate of the impact of the investigators interventions on these domains. Additionally, quality of life, overall symptom burden and satisfaction with care was assessed every 3 months. The investigators assessment of sexual function focused on ED in men, and decreased libido, arousal, dyspareunia, and satisfaction in women. The investigators also conducted monthly assessments of patients' attendance at dialysis, compliance with treatment duration, emergency room visits, and hospitalizations.

After the observational phase, the investigators launched a 12-month intervention phase to compare two interventions. During this phase, the investigators continue these same assessments of pain, sexual dysfunction, depression, quality of life, overall symptom burden and satisfaction with care. The investigators continue to track attendance and compliance with dialysis, emergency room visits, and hospitalizations on a monthly basis. Patients are randomized into one of two study arms by day of dialysis treatment (Monday, Wednesday, and Friday versus Tuesday, Thursday, and Saturday). Sites that only treat patients on a Monday/Wednesday/Friday dialysis schedule are randomized by the time of the dialysis shift within the day, patients on the a.m. shift are randomized to one arm of the study and those on the p.m. shift to the other. One group is randomized to a "feedback intervention" in which renal providers will receive data on the presence and severity of patients' pain, sexual dysfunction, and depression along with algorithms for the treatment of these symptoms (For sexual dysfunction, providers will receive a treatment algorithm for ED and a recommendation to refer women with this symptom for gynecologic care). Treatment decisions will be left at the discretion of the provider(s). The other group has a renal symptom management nurse assess and facilitate the treatment of pain, sexual dysfunction, and depression (management intervention).In this arm, treatment of sexual dysfunction in men will focus on ED, while the symptom management nurse will facilitate referral of women with sexual dysfunction for gynecological care given the lack of pharmacologic therapy.

Study Status: Intervention Phase is completed, analysis is ongoing.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• End Stage Renal Disease
• Sexual Dysfunction, Physiological
• Pain
• Depression

Intervention

• Behavioral: Symptom management nurse intervention
  A symptom management nurse will facilitate the management of pain, sexual dysfunction and depression in patients enrolled in one arm of the study
• Behavioral: Feedback intervention
  Pain, sexual dysfunction and depression will be assessed monthly and feedback will be given to renal providers on the presence and severity of these symptoms. Treatment will be left at the discretion of the renal provider

Study Arms

• Experimental: Symptom management nurse intervention
  This arm of the study will have a symptom management nurse facilitate the management of pain, sexual dysfunction and depression. The nurse will work with the patient's renal provider to implement appropriate symptom alleviating treatment. The intervention is patient specific and entirely dependent on the treatment recommendation made by the symptom management nurse.
  Intervention: Behavioral: Symptom management nurse intervention
• Active Comparator: Feedback intervention
  This arm of the study will have pain, sexual dysfunction and depression assessed monthly with feedback given to renal providers on the presence and severity of these symptoms. Treatment will be left at the discretion of the renal provider. The intervention on symptoms is at the discretion of the renal provider. The interventions implemented were patient specific and consisted of therapies the patient's renal provider decided to implement.
  Intervention: Behavioral: Feedback intervention

Publications *

• Weisbord SD, Shields AM, Mor MK, Sevick MA, Homer M, Peternel J, Porter P, Rollman BL, Palevsky PM, Arnold RM, Fine MJ. Methodology of a randomized clinical trial of symptom management strategies in patients receiving chronic hemodialysis: the SMILE study. Contemp Clin Trials. 2010 Sep;31(5):491-7. doi: 10.1016/j.cct.2010.06.005. Epub 2010 Jul 1.
• Weisbord SD. Sexual dysfunction and quality of life in patients on maintenance dialysis. Semin Dial. 2013 May-Jun;26(3):278-80. doi: 10.1111/sdi.12068. Epub 2013 Mar 5. No abstract available.
• Green JA, Mor MK, Shields AM, Sevick MA, Arnold RM, Palevsky PM, Fine MJ, Weisbord SD. Associations of health literacy with dialysis adherence and health resource utilization in patients receiving maintenance hemodialysis. Am J Kidney Dis. 2013 Jul;62(1):73-80. doi: 10.1053/j.ajkd.2012.12.014. Epub 2013 Jan 24.
• Mor MK, Sevick MA, Shields AM, Green JA, Palevsky PM, Arnold RM, Fine MJ, Weisbord SD. Sexual function, activity, and satisfaction among women receiving maintenance hemodialysis. Clin J Am Soc Nephrol. 2014 Jan;9(1):128-34. doi: 10.2215/CJN.05470513. Epub 2013 Dec 19.
• Weisbord SD, Mor MK, Sevick MA, Shields AM, Rollman BL, Palevsky PM, Arnold RM, Green JA, Fine MJ. Associations of depressive symptoms and pain with dialysis adherence, health resource utilization, and mortality in patients receiving chronic hemodialysis. Clin J Am Soc Nephrol. 2014 Sep 5;9(9):1594-602. doi: 10.2215/CJN.00220114. Epub 2014 Jul 31.
• Green JA, Mor MK, Shields AM, Sevik MA, Palevsky PM, Fine MJ, Arnold RM, Weisbord SD. Renal provider perceptions and practice patterns regarding the management of pain, sexual dysfunction, and depression in hemodialysis patients. J Palliat Med. 2012 Feb;15(2):163-7. doi: 10.1089/jpm.2011.0284.
• Weisbord SD. Female sexual dysfunction in ESRD: an underappreciated epidemic? Clin J Am Soc Nephrol. 2012 Jun;7(6):881-3. doi: 10.2215/CJN.03870412. Epub 2012 May 10. No abstract available.
• Weisbord SD, Mor MK, Green JA, Sevick MA, Shields AM, Zhao X, Rollman BL, Palevsky PM, Arnold RM, Fine MJ. Comparison of symptom management strategies for pain, erectile dysfunction, and depression in patients receiving chronic hemodialysis: a cluster randomized effectiveness trial. Clin J Am Soc Nephrol. 2013 Jan;8(1):90-9. doi: 10.2215/CJN.04450512. Epub 2012 Sep 27.
• Green JA, Mor MK, Shields AM, Sevick MA, Palevsky PM, Fine MJ, Arnold RM, Weisbord SD. Prevalence and demographic and clinical associations of health literacy in patients on maintenance hemodialysis. Clin J Am Soc Nephrol. 2011 Jun;6(6):1354-60. doi: 10.2215/CJN.09761110. Epub 2011 May 5.
• Belayev LY, Mor MK, Sevick MA, Shields AM, Rollman BL, Palevsky PM, Arnold RM, Fine MJ, Weisbord SD. Longitudinal associations of depressive symptoms and pain with quality of life in patients receiving chronic hemodialysis. Hemodial Int. 2015 Apr;19(2):216-24. doi: 10.1111/hdi.12247. Epub 2014 Nov 18.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 14, 2011): 315
• Original Estimated Enrollment (submitted: June 4, 2008): 245
• Actual Study Completion Date: January 2012
• Actual Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Our target population is male and female hemodialysis patients age 18 years or greater who are English speakers.

Exclusion Criteria:

• We will exclude children because they comprise a minority of the dialysis population and their enrollment would require an adult decision maker's consent.
• We will exclude patients who are significantly cognitively impaired and hence, unable to comprehend study surveys.
• Cognitive function will be assessed at baseline using the mini-Cog, a validated measure of cognitive capacity that we have used previously, and patients with scores <3 will be excluded.
• Based on our prior studies, we estimate that approximately 5% of patients will be excluded based on this criterion.
• Similarly, non-English speakers will be excluded.
• Finally, patients undergoing active work-up for living donor kidney transplant, and/or considering transfer to peritoneal dialysis will be excluded as they are less likely to remain on hemodialysis for the duration of the study.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00692419
• Other Study ID Numbers: IIR 07-190
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: VA Office of Research and Development ( US Department of Veterans Affairs )
• Original Responsible Party: Weisbord, Steven - Principal Investigator, Department of Veterans Affairs
• Current Study Sponsor: US Department of Veterans Affairs
• Original Study Sponsor: Same as current

Collaborators

• Dialysis Clinic, Inc.
• Liberty Dialysis, LLC
• DaVita Dialysis

Investigators

• Principal Investigator: Steven D. Weisbord, MD MSc; VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA

• PRS Account: VA Office of Research and Development
• Verification Date: September 2014