Mindfulness in Chronic Kidney Disease

Official title

Sympatho-inhibition With Mindfulness in Chronic Kidney Disease (MIND-CKD)

Overview

This study will test whether mindfulness meditation (MM) improves sympathetic function in chronic kidney disease (CKD) and whether transcutaneous vagus nerve stimulation (tVNS) optimizes the sympatho-inhibitory effects of mindfulness meditation (MM) and restores autonomic balance in CKD patients.

Detailed description

Approximately 30 million people in the US have chronic kidney disease (CKD) and are at 5-15 fold greater risk of cardiovascular (CV) disease and mortality. A major factor contributing to increased CV risk in these patients is chronic elevation of sympathetic nervous system (SNS) activity.

Patients with even minimal decrements in kidney function have significant and substantial increases in SNS activity and reactivity that are independently linked to adverse CV events. The mechanisms underlying SNS overactivity in CKD are multifactorial, and include chronic inflammation and blunted arterial baroreflex sensitivity (BRS). SNS overactivity, in turn, leads to downstream deleterious effects on ambulatory BP profiles characterized by higher daytime BP, and lack of normal reductions in nocturnal BP (i.e. nocturnal nondipping), both of which are independently linked to increased CV risk. Current treatments to combat SNS overactivity are limited to sympatholytic medications such as β-blockers, α-blockers, and clonidine; however, these pharmacologic agents are associated with long-term adverse metabolic consequences such as insulin resistance and hyperlipidemia, and often intolerable side effects such as fatigue, orthostatic hypotension, and rebound hypertension. New therapeutic strategies to safely and effectively ameliorate SNS over-activity are of paramount importance to improve clinical outcomes in this highly prevalent and high-risk patient population.

Mindfulness meditation (MM) may be one such novel, safe, and effective approach at improving hemodynamics and autonomic function in CKD. Prior studies have shown that 8 weeks of mindfulness-based stress reduction (MBSR) lowers BP in a variety of patient groups. Although the mechanisms are poorly understood, studies using indirect measures of SNS activity such as heart rate variability suggest that MM may exert its hemodynamic effects via autonomic modulation.

This study tests whether mindfulness meditation (MM) improves sympathetic function in chronic kidney disease (CKD) and whether transcutaneous vagus nerve stimulation (tVNS) optimizes the sympatho-inhibitory effects of mindfulness meditation (MM) and restores autonomic balance in CKD patients. These study aims are tested with two separate protocols.

Protocol 1 tests the sustained effects of MBSR on SNS function and BP profiles in CKD. Participants will be randomized to 8 weeks of MBSR or a health enhancement program (HEP).

Protocol 2 tests an optimization strategy to enhance the sympatho-inhibitory effects of MM and restore autonomic balance using transcutaneous vagus nerve stimulation (tVNS) in CKD. The vagus nerve, the major effector of the parasympathetic nervous system (PNS), is composed of afferent nerve fibers that connect to the nucleus tractus solitarii (NTS) and other brainstem regions that influence central SNS output and baroreflexes, and efferent nerve fibers that activate the cholinergic anti-inflammatory pathway. Both experimental and human studies have shown promising results that stimulation of the vagus nerve lowers BP reduces SNS activity, improves BRS, and lowers inflammation. Participants with Stage III and IV CKD will be randomized into one of four study arms: MBSR with tVNS, MBSR with sham-tVNS, HEP with tVNS, and HEP with sham-tVNS. Participants will self-administer tVNS or sham-tVNS twice per day for 8 weeks.

Interventions

• Behavioral Mindfulness-based stress reduction (MBSR)
  Mindfulness-based stress reduction (MBSR) is delivered in 8 weekly 2.5-hour group sessions and one day-long retreat that occurs after the 6th session. MBSR teaches to become more aware of thoughts, feelings, and sensations, and to skillfully respond to stressors. Each of the sessions includes education about mindfulness and stress; experiential mindfulness practice, and discussion of participants' experiences with mindfulness practice. Participants learn formal mindfulness practices (e.g., medit
• Behavioral Health enhancement program (HEP)
  8-week health enhancement program (HEP) is designed to provide a structurally parallel, active control intervention to MBSR with health benefits in their own right, while omitting any components of mindfulness. HEP matches MBSR in structure and content, and in parallel to MBSR, consists of music therapy, nutritional education, posture and balance movements, walking and stretching. Work with all practices with group discussion and exercises during an all-day "spa day" will match the all-day retre
• Device Transcutaneous Vagus Nerve Stimulation (tVNS)
  Participants self-administer tVNS twice per day for 8 weeks. tVNS is delivered using a multi-use, hand-held, rechargeable portable device consisting of a rechargeable battery, signal generating and amplifying electronics, and a button for operator control of the stimulation intensity. Conductive gel is applied to the stainless steel round discs on the device and placed vertically on the skin overlying the vagus nerve under the angle of the mandible, between the trachea and sternocleidomastoid mu
• Device Sham-transcutaneous Vagus Nerve Stimulation (tVNS)
  Participants self-administer sham-tVNS twice per day for 8 weeks. Sham stimulation will be delivered using a sham device that is identical in appearance and function, but programmed to produce a lower frequency biphasic signal that can be felt by the participant without actually stimulating the vagus nerve.

Primary outcome measures

• Change in Mean Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency (BF) [Time frame: Baseline, 8 weeks]

Secondary outcome measures (5)

• Change in Daytime Blood Pressure (BP) [Time frame: Baseline, 8 weeks]
• Change in Nocturnal Dipping of Blood Pressure (BP) [Time frame: Baseline, 8 weeks]
• Change in Heart Rate Assessed by 24-hour EKG Monitoring [Time frame: Baseline, 8 weeks]
• Change in Baroreflex Sensitivity (BRS) Among Protocol 2 Participants [Time frame: Baseline, 8 weeks]
• Change in Tumor Necrosis Factor (TNF) Level Among Protocol 2 Participants [Time frame: Baseline, 8 weeks]

Eligibility criteria

Inclusion criteria

• stages III and IV CKD as defined by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation
• stable renal function (no greater than a decline of eGFR of 1 cc/min/1.73 m2 per month over the prior 3 months)

Exclusion criteria

• severe CKD (eGFR<15 cc/min)
• diabetic neuropathy
• autonomic dysfunction
• any serious disease that might influence survival
• anemia with hemoglobin <10 g/dL
• treatment with central α-agonists or monoamine oxidase (MAO) inhibitors
• myocardial infarction or cerebrovascular accident within the past 6 months
• uncontrolled hypertension (BP≥170/100 mm Hg)
• low BP (BP<100/50 mm Hg)
• bradycardia (HR<55 beats/min)
• ongoing drug or alcohol abuse (defined as >2 drinks/day in men, and >1 drink/day in women)
• surgery within the past 3 months
• adjustment of antihypertensive medications within the past month
• pregnancy or plans to become pregnant
• psychosis
• suicidal ideation
• implanted electronic or metallic device such as a pacemaker
• implanted hearing aid, bone plate, carotid stent, bone screw at or near the neck
• carotid atherosclerosis
• concurrent use of another stimulating device such as a transcutaneous electrical nerve stimulation (TENS) unit

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• Atlanta VA Medical Center — Atlanta

Publications

• Jeong J, Hu Y, Zanuzzi M, DaCosta D, Sabino-Carvalho JL, Li S, Park J. Autonomic modulation with mindfulness-based stress reduction in chronic kidney disease: a randomized controlled trial. J Physiol. 2025 Jan;603(2):489-505. doi: 10.1113/JP287321. Epub 2024 Dec 18. PMID 39693497

Identifiers

NCT: NCT04099992 · IRB00110956 · 5R61AT010457 · 4R33AT010457

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗