A Physiologic Comparison of Two Approaches to Treating Peripheral Neuropathy

NCT05577390 | Recruiting

• 1 other identifier: 5220363
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Diabetic peripheral neuropathy is one of the most common and costly microvascular complications of diabetes impacting more than 50% of patients and costing more than 10.1 billion dollars annually. Intraneural Facilitation Therapy (INF® Therapy) is a non-invasive technique that has shown to improve balance and pain in patients with Type 2 Diabetic Peripheral Neuropathy (T2DPN); however, the underlying physiological mechanisms need further understanding. The purpose of this study is to investigate the physiological mechanisms behind two approaches to treating T2DPN, INF® Therapy and standard physical therapy. Eligible subjects presenting with diabetic neuropathy symptoms will be recruited and referred to the Loma Linda University Health's Neuropathic Therapy Center. Forty patients will be evenly randomized into two groups: an INF® Therapy Treatment group and standard physical therapy treatment group. Subjects will participate in 11 study visits over a period of 6 weeks. Non-invasive assessments will measure neuropathy pain, heart rate variability, neuropathy severity, blood oxygen levels, and blood flow under the skin. Lab draws will measure inflammation levels in the blood and how well blood sugar levels have been maintained over a period of about 3 months. Descriptive statistics and repeated measures ANOVA will be used to analyze data and answer the research questions. The findings of this study will provide a better understanding of how INF® Therapy and standard physical therapy work, subsequently improving non-invasive treatment methods for T2DPN patients.

Conditions

Peripheral Neuropathy With Type 2 Diabetes

Keywords

Intraneural Facilitation Therapy; Type 2 Diabetes; Neuropathy; Heart rate variability

Outcome Measures

Primary Outcomes (1)

• The Impact of INF® Therapy and Standard Physical Therapy on Heart Rate Variability

  This is a composite measurement combining electrocardiogram and Welltory App measurements. Heart rate variability (HRV) is the variation in the time interval between consecutive heartbeats and can be used to assess the current state of the nervous system. HRV measures will include LF, HF, LF/HF ratio, SDNN, SDANN, RMSSD, and NN50. The calculation of these variables allows HRV to be quantified. A normal result is between 25 to 50 milliseconds while an abnormal result is less than or greater than that range.

  Through study completion, an average of 6 weeks.

Secondary Outcomes (3)

• The impact of INF® Therapy and Standard Physical Therapy on neuropathy severity

  Through study completion, an average of 6 weeks.

• The impact of INF® Therapy and Standard Physical Therapy on blood flow

  Through study completion, an average of 6 weeks.

• The impact of INF® Therapy and Standard Physical Therapy on inflammation

  Through study completion, an average of 6 weeks.

Study Arms (2)

Intraneural Facilitation Therapy Treatment Group

EXPERIMENTAL

Subjects will receive nine 60-minute INF® Therapy Treatments during sessions 2 through 10. INF® Therapy is a non-invasive treatment that helps eliminate pain, tingling, numbness, and other symptoms that come with neuropathy.

Other: Intraneural Facilitation Therapy Treatment

Standard Physical Therapy Treatment Group

EXPERIMENTAL

Subjects will receive nine 60-minute standard physical therapy treatments during sessions 2 through 10.

Other: Standard Physical Therapy Treatment

Interventions

Intraneural Facilitation Therapy Treatment OTHER

Intraneural Facilitation Therapy uses three manual holds to bias blood flow to closed endoneurial capillaries. The first is the facilitation hold, which is thought to pressurize the nervous system and bias circulation from the artery into the epineurium. This hold stretches the nerve further than the artery, increasing the amount of elastin in the artery and enlarging the opening of the arterial junction increasing blood into the epineurium. The secondary hold then increases epineurial blood into the transperineurial vessels increasing pressure into the endoneurial capillaries of the site being treated. The third hold, known as the sub hold, encourages blood flow through ischemic endoneurial capillaries that have increased resistance/pressure through the application of Bernoulli's principle. The series of stretches will be repeated on the affected side for the treatment duration.

Intraneural Facilitation Therapy Treatment Group

Standard Physical Therapy Treatment OTHER

The standard physical therapy treatment includes muscle stretching, balance, and strengthening exercises known to improve neuropathy symptoms.

Standard Physical Therapy Treatment Group

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between the ages of 45 and 85
• Moderate to severe type II diabetic neuropathy with one or more symptoms including: numbness, tingling, burning, sharp pain, and/or increased sensitivity.
• Diagnosis confirmed by a physician.
• Cellphone access with Android 5.0 and up or iOS 14.0 or later.

You may not qualify if:

• Subjects with a medical condition predisposing them to medical decline during the next 6 months will be excluded from the study. Examples include:
• Chemotherapy
• Radiation
• Lower extremity amputations
• Open wounds
• Documented active drug and or alcohol misuse
• Chronic liver disease
• Active inflammations
• Other types of neuropathies not associated with diabetes including B12 deficiency and Charcot Marie Tooth
• Morbid obesity
• Pregnancy.
• Taking beta blockers
• Unable to maintain steady fingers or operate a cellphone
• Smoking or ingesting marijuana
• Having a pacemaker

Sponsors & Collaborators

• Loma Linda University: lead

Study Sites (1)

Loma Linda University Health Neuropathic Therapy Center

Loma Linda, California, 92350, United States

RECRUITING

Related Publications (17)

• Heart rate variability. Standards of measurement, physiological interpretation, and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Eur Heart J. 1996 Mar;17(3):354-81. No abstract available.

  PMID: 8737210 BACKGROUND

• Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, Colagiuri S, Guariguata L, Motala AA, Ogurtsova K, Shaw JE, Bright D, Williams R; IDF Diabetes Atlas Committee. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019 Nov;157:107843. doi: 10.1016/j.diabres.2019.107843. Epub 2019 Sep 10.

  PMID: 31518657 BACKGROUND

• Feldman EL, Callaghan BC, Pop-Busui R, Zochodne DW, Wright DE, Bennett DL, Bril V, Russell JW, Viswanathan V. Diabetic neuropathy. Nat Rev Dis Primers. 2019 Jun 13;5(1):41. doi: 10.1038/s41572-019-0092-1.

  PMID: 31197153 BACKGROUND

• Gordois A, Scuffham P, Shearer A, Oglesby A, Tobian JA. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care. 2003 Jun;26(6):1790-5. doi: 10.2337/diacare.26.6.1790.

  PMID: 12766111 BACKGROUND

• Gore M, Brandenburg NA, Dukes E, Hoffman DL, Tai KS, Stacey B. Pain severity in diabetic peripheral neuropathy is associated with patient functioning, symptom levels of anxiety and depression, and sleep. J Pain Symptom Manage. 2005 Oct;30(4):374-85. doi: 10.1016/j.jpainsymman.2005.04.009.

  PMID: 16256902 BACKGROUND

• Hicks CW, Selvin E. Epidemiology of Peripheral Neuropathy and Lower Extremity Disease in Diabetes. Curr Diab Rep. 2019 Aug 27;19(10):86. doi: 10.1007/s11892-019-1212-8.

  PMID: 31456118 BACKGROUND

• Callaghan BC, Gallagher G, Fridman V, Feldman EL. Diabetic neuropathy: what does the future hold? Diabetologia. 2020 May;63(5):891-897. doi: 10.1007/s00125-020-05085-9. Epub 2020 Jan 23.

  PMID: 31974731 BACKGROUND

• Alshahrani A, Bussell M, Johnson E, Tsao B, Bahjri K. Effects of a Novel Therapeutic Intervention in Patients With Diabetic Peripheral Neuropathy. Arch Phys Med Rehabil. 2016 May;97(5):733-8. doi: 10.1016/j.apmr.2015.12.026. Epub 2016 Jan 22.

  PMID: 26808781 BACKGROUND

• Sun PC, Kuo CD, Chi LY, Lin HD, Wei SH, Chen CS. Microcirculatory vasomotor changes are associated with severity of peripheral neuropathy in patients with type 2 diabetes. Diab Vasc Dis Res. 2013 May;10(3):270-6. doi: 10.1177/1479164112465443. Epub 2012 Dec 14.

  PMID: 23241514 BACKGROUND

• Zheng H, Sun W, Zhang Q, Zhang Y, Ji L, Liu X, Zhu X, Ye H, Xiong Q, Li Y, Lu B, Zhang S. Proinflammatory cytokines predict the incidence of diabetic peripheral neuropathy over 5 years in Chinese type 2 diabetes patients: A prospective cohort study. EClinicalMedicine. 2020 Dec 23;31:100649. doi: 10.1016/j.eclinm.2020.100649. eCollection 2021 Jan.

  PMID: 33385123 BACKGROUND

• Lockhart CJ, McCann AJ, Pinnock RA, Hamilton PK, Harbinson MT, McVeigh GE. Multimodal functional and anatomic imaging identifies preclinical microvascular abnormalities in type 1 diabetes mellitus. Am J Physiol Heart Circ Physiol. 2014 Dec 15;307(12):H1729-36. doi: 10.1152/ajpheart.00372.2014. Epub 2014 Oct 3.

  PMID: 25281566 BACKGROUND

• McVeigh GE, Morgan DR, Allen P, Trimble M, Hamilton P, Dixon LJ, Silke B, Hayes JR. Early vascular abnormalities and de novo nitrate tolerance in diabetes mellitus. Diabetes Obes Metab. 2002 Sep;4(5):336-41. doi: 10.1046/j.1463-1326.2002.00220.x.

  PMID: 12190997 BACKGROUND

• Selvarajah D, Wilkinson ID, Fang F, Sankar A, Davies J, Boland E, Harding J, Rao G, Gandhi R, Tracey I, Tesfaye S. Structural and Functional Abnormalities of the Primary Somatosensory Cortex in Diabetic Peripheral Neuropathy: A Multimodal MRI Study. Diabetes. 2019 Apr;68(4):796-806. doi: 10.2337/db18-0509. Epub 2019 Jan 7.

  PMID: 30617218 BACKGROUND

• Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes Care. 2003 May;26(5):1553-79. doi: 10.2337/diacare.26.5.1553.

  PMID: 12716821 BACKGROUND

• Pop-Busui R, Backlund JC, Bebu I, Braffett BH, Lorenzi G, White NH, Lachin JM, Soliman EZ; DCCT/EDIC Research Group. Utility of using electrocardiogram measures of heart rate variability as a measure of cardiovascular autonomic neuropathy in type 1 diabetes patients. J Diabetes Investig. 2022 Jan;13(1):125-133. doi: 10.1111/jdi.13635. Epub 2021 Aug 14.

  PMID: 34309223 BACKGROUND

• Iannetta D, Inglis EC, Soares RN, McLay KM, Pogliaghi S, Murias JM; CAPES scholarship holder. Reliability of microvascular responsiveness measures derived from near-infrared spectroscopy across a variety of ischemic periods in young and older individuals. Microvasc Res. 2019 Mar;122:117-124. doi: 10.1016/j.mvr.2018.10.001. Epub 2018 Oct 4.

  PMID: 30292692 BACKGROUND

• Brown CD, Davis HT, Ediger MN, Fleming CM, Hull EL, Rohrscheib M. Clinical assessment of near-infrared spectroscopy for noninvasive diabetes screening. Diabetes Technol Ther. 2005 Jun;7(3):456-66. doi: 10.1089/dia.2005.7.456.

  PMID: 15929677 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Mark Bussell, DPT, OCS

  Loma Linda University Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark Bussell, DPT, OCS

CONTACT

909-558-6799; ntcresearch@llu.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Single-blinded study. Subjects will be randomly assigned to one of two treatment groups. Treating therapists will be informed of the study arm assignment. The physical therapist performing the pre and post evaluation measurements will be different than the treating therapists and blinded to the study arm assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Two arms: One INF® Therapy Treatment group and One standard physical therapy treatment group

Study Record Dates

• First Submitted: September 27, 2022
• First Posted: October 13, 2022
• Study Start: January 8, 2024
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: November 19, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available indefinitely from six months post-manuscript publication.
• Access Criteria: Data stored on our GitHub repository will be made available to clinicians and researchers after reaching out to the project leaders for access to the data repository.

Locations

US (1)