Concurrent Training vs Soleus Push-Ups on Neurogenesis-Related Biomarkers in Diabetic Neuropathy Patients
Comparative Effects of Concurrent Training and Soleus Push-Ups on Neurogenesis-Related Biomarkers in Patients With Diabetic Peripheral Neuropathy: A Randomized Controlled Trial
1 other identifier
interventional
99
1 country
1
Brief Summary
This study will examine how two types of exercise programs affect nerve health in people with diabetic peripheral neuropathy. Diabetic peripheral neuropathy is a common complication of type 2 diabetes that can cause numbness, pain, balance problems, and reduced quality of life. Exercise is often recommended for people with diabetes, but it is not yet clear which types of exercise are most effective for improving nerve function. In this randomized controlled trial, participants with type 2 diabetes and confirmed peripheral neuropathy will be assigned to one of three groups. One group will perform a combined program of aerobic and resistance exercises (concurrent training). Another group will perform soleus push-up exercises, a seated ankle movement designed to activate the soleus muscle and improve glucose metabolism. The third group will continue with standard diabetes care and general lifestyle advice without a structured exercise program. The study will evaluate whether these exercise interventions influence biological markers related to nerve repair and neuroplasticity, including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and the Schwann cell marker S100B. In addition, the study will assess changes in neuropathy symptoms, balance and postural stability, blood sugar control, and quality of life. Participants will complete assessments before the intervention and again during follow-up after the exercise program. The findings of this study may help identify effective and feasible exercise strategies to support nerve health, improve physical function, and reduce the impact of diabetic peripheral neuropathy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for not_applicable
Started Sep 2026
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 15, 2026
CompletedFirst Posted
Study publicly available on registry
June 30, 2026
CompletedStudy Start
First participant enrolled
September 1, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2027
Study Completion
Last participant's last visit for all outcomes
December 1, 2027
June 30, 2026
June 1, 2026
1 year
April 15, 2026
June 23, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
BDNF (Brain-Derived Neurotrophic Factor)
Serum Brain-Derived Neurotrophic Factor (BDNF) concentration will be measured quantitatively using a commercially available enzyme-linked immunosorbent assay (ELISA) kit at baseline, 4 weeks, and 8 weeks. BDNF is a neurotrophic factor involved in neuronal survival, synaptic plasticity, and exercise-induced neuroplasticity. Changes in circulating BDNF levels will be used as a primary biomarker of exercise-induced neuroplasticity and neurogenesis-related biological activity. Higher serum BDNF concentrations are considered indicative of greater neurotrophic activity and potential enhancement of neuroplastic processes.
From enrollment to 4 weeks and then to the end of treatment at 8 weeks.
NGF (Nerve Growth Factor)
Serum Nerve Growth Factor (NGF) concentration will be measured quantitatively using a commercially available enzyme-linked immunosorbent assay (ELISA) kit at baseline, 4 weeks, and 8 weeks. NGF is a key neurotrophic factor involved in the survival, maintenance, and regeneration of peripheral neurons. It plays a fundamental role in peripheral nerve repair and axonal regeneration following nerve injury. Changes in circulating NGF levels will be used as a primary biomarker of peripheral nerve regeneration and neuroregeneration-related biological activity. Higher serum NGF concentrations are considered indicative of enhanced neurotrophic support and regenerative potential of peripheral nerves.
From enrollement to 4 weeks and then after 8 weeks of intervention
S100B (Schwann Cell Marker)
Serum S100 Calcium-Binding Protein B (S100B) concentration will be measured quantitatively using a commercially available enzyme-linked immunosorbent assay (ELISA) kit at baseline, 4 weeks, and 8 weeks. S100B is a calcium-binding protein that is expressed by Schwann cells in the peripheral nervous system and plays an important role in peripheral nerve repair, remyelination, and axonal regeneration. Changes in circulating S100B levels will be used as a primary biomarker of Schwann cell activity and peripheral nerve regeneration. Higher serum S100B concentrations are considered indicative of increased Schwann cell-mediated neuroregenerative activity.
From enrollment to 4 weeks and then after 8 weeks of intervention
Secondary Outcomes (8)
Michigan Neuropathy Screening Instrument (MNSI)
From enrollment to 4 weeks and then to the end of treatment at 8 weeks.
Vibration perception threshold (VPT)
From enrollment to 4 weeks and then to the end of treatment at 8 weeks.
Balance and Gait Mobile Application
From enrollment to 4 weeks and then to the end of treatment at 8 weeks.
Glycated Hemoglobin (HbA1c)
From enrollment to 4 weeks and then to the end of treatment at 8 weeks.
Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN)
From enrollment to 4 weeks and then to the end of treatment at 8 weeks.
- +3 more secondary outcomes
Study Arms (3)
Concurrent Training Group (CT)
ACTIVE COMPARATORParticipants will undergo a combined aerobic and resistance exercise program.
Soleus Push-Up Group (SPU)
EXPERIMENTALParticipants will perform seated plantar-flexion exercises targeting the soleus muscle, using a controlled movement protocol modeled after the soleus push-up method.
Control Group
NO INTERVENTIONParticipants will receive standard diabetes care and general lifestyle advice without structured exercise intervention.
Interventions
Seated plantar-flexion exercises targeting the soleus muscle, using a controlled movement protocol
Combined aerobic and resistance exercise program.
Eligibility Criteria
You may qualify if:
- Age 40-65 years
- Diagnosed Type 2 Diabetes Mellitus (T2DM) Confirmed diagnosis of T2DM for at least 5 years.
- Confirmed Diabetic Peripheral Neuropathy (DPN)
- Diagnosis is based on clinical evaluation and scoring tools such as:
- Michigan Neuropathy Screening Instrument (MNSI) Cut-off value of ≥4 for Part A (History)(104) Cut-off value of ≥2 from Part B (Examination)(105)
- Vibration Pressure Threshold (≥25 Volts)(106)
- HbA1c between 6.5% and 9.0% Reflecting moderate glycemic control, patients with extremely poor control were excluded for safety.
- Stable medication regimen No changes in antidiabetic, antihypertensive, or neuropathy medications in the past 3 months.
- Sedentary or low physical activity level Based on standard questionnaires (International Physical Activity Questionnaire - IPAQ), not currently engaged in structured exercise programs.
- Ability to walk independently To ensure safety during aerobic or resistance exercise (for Group A).
- Able to understand and follow instructions
- Consent to participate and comply with study protocol
- Written informed consent, obtained before randomization
You may not qualify if:
- History of recent cardiovascular events Includes myocardial infarction, stroke, or any cardiac intervention within the past 6 months.
- Uncontrolled hypertension Blood pressure ≥160/100 mmHg at rest.
- Severe musculoskeletal disorders or physical disability Including joint deformities, fractures, or amputation that limit the ability to perform exercise.
- Severe diabetic foot ulcers or active lower limb infection Increases risk during lower limb activity or exercise.
- End-stage renal disease (CKD stage 4 or higher) Associated systemic complications may confound study outcomes or affect safety.
- Severe retinopathy or proliferative diabetic eye disease Exercise may pose risks such as retinal hemorrhage.
- Current Smoker, tobacco or alcohol consumer. That may affect the blood biomarkers.
- Cognitive impairment or psychiatric disorders That may affect understanding, compliance, or safety during exercise.
- Participation in a structured exercise program within the last 3 months To avoid training-induced bias and ensure a sedentary baseline.
- Chronic inflammatory or autoimmune conditions Conditions like rheumatoid arthritis or lupus may alter neurotrophic biomarkers.
- Use of medications affecting neurogenesis or metabolism Such as corticosteroids, antipsychotics, or immunosuppressants.
- Diagnosed sleep disorder
- That may affect the outcomes of the intervention.
- Pregnancy or lactation Due to altered physiology and ethical concerns.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Pakistan Railways General Hospital and Mediplex Healthcare Center
Rawalpindi, 46210, Pakistan
Related Publications (1)
Jamali A, Shahrbanian S, Morteza Tayebi S. The Effects of Exercise Training on the Brain-Derived Neurotrophic Factor (BDNF) in the Patients with Type 2 Diabetes: A Systematic Review of the Randomized Controlled Trials. J Diabetes Metab Disord. 2020 May 6;19(1):633-643. doi: 10.1007/s40200-020-00529-w. eCollection 2020 Jun.
PMID: 32550216BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Muhammad Ashar Rafi, MS-NMPT
Riphah International University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 15, 2026
First Posted
June 30, 2026
Study Start (Estimated)
September 1, 2026
Primary Completion (Estimated)
September 1, 2027
Study Completion (Estimated)
December 1, 2027
Last Updated
June 30, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will not share
Individual participant data collected during the trial will not be made publicly available. Study findings will be disseminated through peer-reviewed publications and conference presentations. All data will remain securely stored by the research team in accordance with institutional policies and ethical guidelines.