Cognitive-Behavioral Therapy for Sleep Disturbance in Patients Undergoing Hemodialysis

Sleep disturbance is common in patients with renal disease. According to previous studies, it occurs in more than 50% of chronic kidney disease (CKD) patients and those undergoing dialysis. 1, 2 Insomnia, restless legs syndrome (RLS), daytime sleepiness, and sleep apnea syndrome are common complaints; such sleep disturbances significantly affect the quality of life, overall morbidity, hospitalization, and mortality. 3-5 The main remedy for sleep disturbances, hypnotics, have notable side effects such as daytime sleepiness, psychological dependence, and drug-to-drug interactions, which make these drugs less than an optimal therapy. 6 Cognitive-behavioral therapy (CBT), the most widely used psychological intervention for insomnia, combines cognitive strategies such as stimulus control and relaxation training and has been proven to be effective for chronic insomnia in the elderly, cancer patients, and chronic pain sufferers7, 8. In most published articles CBT has been reported be superior to pharmacological and other behavioral therapies.9 In our previous investigation10, we found that the CBT was effective in PD patients with sleep disturbance presented with declined of Pittsburgh Sleep Quality Index (PSQI) and Fatigue Severity Scale (FSS); furthermore, the inflammatory cytokines, such as IL-1β, IL-18, TNF-α also declined after CBT in those insomnias PD patients. In previous studies, changes in cytokine release correlated with insomnia in patients undergoing hemodialysis11 or with breast cancer.12 Nevertheless, the effectiveness of CBT of sleep disturbance in insomnias HD patients is still not known.

In this study, we investigated the effectiveness of CBT for treatment of HD patients with insomnia by assessing changes in sleep quality subjectively through self-report questionnaires. The purpose of this study was to identify new therapeutic options for sleep disorders beyond hypnotics in HD patients. Because the association of sleep disturbance, oxidative stress and autonomic dysfunction in general population and patient with sleep apnea were demonstrated in previous investigations, we also investigate the possible impacts of CBT on the oxidative stress, autonomic dysfunction in these patients.

This study is designed to:

1. To evaluate the effectiveness of CBT for sleep disturbance in maintenance HD patients.
2. To evaluate the possible impacts of CBT on inflammatory cytokines, oxidative stress and autonomic dysfunction in insomnias HD patients. .
3. To compare the systemic inflammation, oxidative stress and autonomic dysfunction in HD patients with and without sleep disturbance.

Study designs and methods Eighty ESRD patients undergoing maintenance hemodialysis (HD) for more than 6 months with subjective complaint of sleep disturbance and screening PSQI ≥ 5 will be recruited for the investigation. Besides, 40 ESRD patients undergoing HD for more than 6 months without sleep disturbance will also be recruited as the population-base control group. Insomnias HD patients (N=80) will be randomized into interventional group (CBT group) and control group in 1:1 ratio in the following 6-week trial.

All participants (N=120) will receive questionnaires including Pittsburgh Sleep Quality Index (PSQI), Fatigue Severity Scale (FSS), Beck depression index (BDI) and the International Index of Erectile Function (IIEF) for men and the Index of Female Sexual Function (IFSF) and check-ups of baroreflex sensitivity (BRS) for autonomic dysfunction before the trial. Also, all of them will get fasting blood sampling at the initiation of trial in the morning before mid-week HD section for analysis of inflammatory cytokines (serum IL-1β, IL-18, and TNF-α levels) and oxidative stress (TBARS, Total antioxidant status and serum 8-OHdG). Participants with sleep disturbance will be randomized into CBT group and control group in 1:1 ratio and all of them receive sleep hygiene education before the trial. Participants who randomized into the CBT group will receive 6 1-hour weekly treatment sessions of CBT during the 6-week period. Participants who received hypnotics chronically before being recruited were maintained at the same dose of hypnotics during the therapy. After the 6-week trail, all participants will receive PSQI, FSS, BDI, IIEF, IFSF and BRS again and 2nd blood sampling for analysis of inflammatory cytokine and oxidative stress again. All the questionnaires, BRS and analyses of inflammatory cytokine and oxidative stress will be performed again 3 months after the trial for the long-term follow-up analysis. The details of investigation are demonstrated in Figure 1.