Clinical trial NCT04099992: Mindfulness in Chronic Kidney Disease
Official title: Sympatho-inhibition with Mindfulness in Chronic Kidney Disease (MIND-CKD)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Chronic Kidney Diseases
Keywords: Mindfulness
Transcutaneous Vagus Nerve Stimulation
tVNS
Sympatho-inhibitory effects
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
First posted: 2019-09-23
Enrollment: 150
Sex: ALL
Minimum age (years): 40
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Protocol 1 (R61): 50 CKD participants will be randomized to MBSR (N=25) versus an active control intervention (health enhancement program; N=25).

Protocol 2 (R33): 100 CKD participants will be randomized to MBSR+tVNS (n=25), MBSR+sham-tVNS (n=25), HEP+tVNS (n=25), and HEP+sham-tVNS (n=25).
Primary purpose: TREATMENT

Brief summary: 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.

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

Primary outcomes:
measure: Change in Mean Muscle Sympathetic Nerve Activity (MSNA) Burst Frequency (BF)
timeFrame: Baseline, 8 weeks
Secondary outcomes:
measure: Change in Daytime Blood Pressure (BP)
timeFrame: Baseline, 8 weeks
measure: Change in Nocturnal Dipping of Blood Pressure (BP)
timeFrame: Baseline, 8 weeks
measure: Change in Heart Rate Assessed by 24-hour EKG Monitoring
timeFrame: Baseline, 8 weeks
measure: Change in Baroreflex Sensitivity (BRS) Among Protocol 2 Participants
timeFrame: Baseline, 8 weeks
measure: Change in Tumor Necrosis Factor (TNF) Level Among Protocol 2 Participants
timeFrame: Baseline, 8 weeks
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Atlanta VA Medical Center
state: Georgia
Study officials:
affiliation: Emory University
name: Jeanie Park
role: PRINCIPAL_INVESTIGATOR
References: