Small-fiber Neuropathy in Chronic Kidney Disease

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01078857
Recruitment Status : Unknown
Verified February 2010 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : March 2, 2010
Last Update Posted : March 2, 2010
Information provided by:
National Taiwan University Hospital

Brief Summary:
Neurological dysfunction is a common complication of late stage chronic kidney disease (CKD) and peripheral nerve system is often involved in such complication. Sensory disturbances such as paresthesia and hypoesthesia are the predominant symptoms in uremic polyneuropathy and it is traditionally thought the uremic polyneuropathy mainly involve large-diameter sensory nerves. However in uremic patients the abnormal thermal thresholds, the sensory symptoms like numbness, burning, paradoxical heat, cold or freezing, and pain, and the frequent symptoms of autonomic dysfunction suggest that small-fiber neuropathy should be a clinical entity in patients of CKD. But there are still few investigations with emphasis on the changes of small-fiber nerves in CKD, and little is known about the characteristics and mechanism of small-fiber neuropathy in CKD. Skin biopsy with evaluation of epidermal nerve density and the morphology of epidermal nerves and the subepidermal nerve plexus is an effective and minimally invasive test for assessment of small-fiber neuropathy. Contact heat evoked potential (CHEP) recording the brain responses evoked by contact heat stimuli on the skin is a non-invasive technique to investigate the thermo-nociceptive pathways mediated by small-fiber nerves. In the current study, we will use an integrated approach by combining the skin biopsy, quantitative sensory testing, autonomic function tests, and CHEP to investigate the pathological, psychophysical and physiological aspects of small-fiber neuropathy in patients of CKD. The aims of the current study is to address the following issues: (1) the changes of small fiber nerves in uremia and CKD of different stage; (2) the correlation of skin innervation with clinical manifestations, thermal thresholds, and autonomic function; (3) the influence of dialysis therapy, the type of dialysis therapy, or renal transplantation on the small fiber neuropathy in uremia; (4) the roles of blood chemical substances, metals, and endocrine profiles on the development of small-fiber neuropathy; (5) the relationship between the small-fiber neuropathy and pruritus or restless leg syndrome; and (6) the pathological and physiological correlates of painful symptoms by skin biopsy and CHEP in CKD related neuropathy. The results of the study will provide important insights in the understanding of the pathogenesis, and the prevention and new treatments of small-fiber neuropathy in CKD.

Condition or disease Intervention/treatment
Small-Fiber Neuropathy Chronic Kidney Disease Other: Skin biopsy

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: Small-fiber Neuropathy in Chronic Kidney Disease
Study Start Date : February 2009
Estimated Primary Completion Date : August 2012

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Intervention Details:
    Other: Skin biopsy
    A 3-mm-diameter skin biopsy punch was taken at the lateral side of the distal leg and fixed in 4% paraformaldehyde overnight. Sections of 50 m perpendicular to the dermis were cut on a sliding microtome, quenched with 1% H2O2 in methanol, and blocked with 5% normal goat serum. Sections were incubated with rabbit antiserum to protein gene product 9.5 (PGP 9.5, UltraClone, Isle of Wight, UK, 1:1000) overnight. PGP 9.5 is a ubiquitin carboxyl hydrolase, which labels myelinated and unmyelinated nerve fibers in the peripheral nervous system. Sections were then incubated with biotinylated goat anti-rabbit immunoglobulin G (Vector, Burlingame, CA) for 1 h and the avidin-biotin complex (Vector) for another hour. The reaction product was demonstrated using chromogen SG (Vector).

Primary Outcome Measures :
  1. The pathology of skin biopsy [ Time Frame: within 3 months after inclusion ]
  2. Intraepidermal fiber density [ Time Frame: within 3 months after inclusion ]
  3. Autonomic function [ Time Frame: within 3 months after inclusion ]

Secondary Outcome Measures :
  1. Function of small-fiber sensory nerve [ Time Frame: within 3 months after inclusion ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • The patients should fulfill the criteria of CKD according to renal function study and the patients of end-stage renal disease should receive regular dialysis therapy and follow-up at outpatient clinics.
  • For disease comparison, patients with peripheral neuropathy of variable etiologies will also be recruited.

Exclusion Criteria:

  • Poor control DM,
  • Severe heart failure,
  • Bleeding tendency,
  • Severe lung disease with respiratory distress,
  • Severe infection,
  • Alcoholism,
  • Amyloidosis,
  • Poor wound healing history.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01078857

Contact: Sung-Tsang Hsieh, PhD 886-2-23123456 ext 88182

National Taiwan University Hospital Recruiting
Taipei, Taiwan, 10002
Contact: Sung-Tsang Hsieh, PhD    886-2-23123456 ext 88182   
Principal Investigator: Chi-Chao Chao, MD         
Sponsors and Collaborators
National Taiwan University Hospital
Study Director: Sung-Tsang Hsieh National Taiwan University Hospital

Responsible Party: Chi-Chao, Chao, Department of Neurology, National Taiwan University Hospital Identifier: NCT01078857     History of Changes
Other Study ID Numbers: 200812088R
First Posted: March 2, 2010    Key Record Dates
Last Update Posted: March 2, 2010
Last Verified: February 2010

Keywords provided by National Taiwan University Hospital:
Chronic kidney disease
Small-fiber neuropathy
Skin biopsy
Contact heat evoked potential
Autonomic neuropathy
Neuropathy in late stage chronic kidney disease

Additional relevant MeSH terms:
Kidney Diseases
Renal Insufficiency, Chronic
Peripheral Nervous System Diseases
Small Fiber Neuropathy
Urologic Diseases
Renal Insufficiency
Neuromuscular Diseases
Nervous System Diseases