n-3 Polyunsaturated Fatty Acids to Prevent and Treat Diabetic Neuropathy

NCT05145452 | Terminated DMC

• 1 other identifier: 2097478
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

Sensorimotor neuropathy (SMN) and cardiovascular autonomic neuropathy (CAN) are the most common complications of type 2 diabetes (T2D). SMN affects \~30% of people with T2D and CAN \~20%. SMN causes pain, impairs and limits physical activity, and increases the risk for physical disability, complications (such as foot ulcerations), and premature mortality. Moreover, both motor and sensory nerve function are important regulators of muscle function; impaired myofiber innervation causes myofiber loss, muscle fat infiltration, and increases the risk of age-associated sarcopenia and falls. CAN often goes unrecognized because it presents with non-specific symptoms, such as resting tachycardia and fixed heart rate, exercise intolerance, and orthostatic hypotension. However, CAN is a serious problem because it increases the risk for cardiovascular events and mortality several-fold. Both SMN and CAN have long been considered a consequence of T2D, but it is now becoming clear that they precede the diagnosis of T2D and are already detectable in people with prediabetes, especially those with impaired glucose tolerance. Treatments for both SMN and CAN focus on symptom management because there are no effective therapeutics that target the underlying neuropathy. The results from studies conducted in animal models suggest fish oil-derived n-3 polyunsaturated fatty acids (n-3 PUFA) may have therapeutic effects for people with SMN and CAN. The purpose of this proposal is to conduct a randomized controlled trial to test the hypothesis that dietary supplementation with fish oil-derived n-3 PUFA improves sensorimotor and cardiovascular autonomic functions in people with impaired glucose tolerance. Forty 55-80 year old men and women with impaired glucose tolerance (plasma glucose 2 h after a 75 g glucose challenge ≥140 mg/dl) and evidence of SMN (assessed as epidermal nerve fiber density) will be randomized to either receive fish oil-derived n-3 PUFA (4.2 g per day; n=20) or placebo (n=20) for six months. Sensorimotor and cardiovascular autonomic function will be evaluated after three and 6 months of the interventions.

Conditions

Diabetic Neuropathies

Outcome Measures

Primary Outcomes (3)

• Sensorimotor function

  Nerve conduction velocity

  Change from baseline to 6 months

• Cardiovascular autonomic function

  Heart rate variability

  Change from baseline to 6 months

• Muscle endurance

  Decline in torque during repeat muscle contraction

  Change from baseline to 6 months

Secondary Outcomes (6)

• Glucose tolerance

  Change from baseline to 6 months

• Insulin sensitivity

  Change from baseline to 6 months

• Beta cell function

  Change from baseline to 6 months

• Plasma triglyceride concentration

  Change from baseline to 6 months

• Muscle strength

  Change from baseline to 6 months

Study Arms (3)

Intervention Group

EXPERIMENTAL

Subjects randomized to n-3 PUFA will receive a total of 4.2 g/d of fish oil.

Dietary Supplement: Fish-oil derived n-3 polyunsaturated fatty acids

Placebo Group

PLACEBO COMPARATOR

Subjects randomized to placebo will receive 4.2 g/d sunflower oil.

Dietary Supplement: Fish-oil derived n-3 polyunsaturated fatty acids

Control group

NO INTERVENTION

Subjects assigned to the control group will be tested once

Interventions

Fish-oil derived n-3 polyunsaturated fatty acids DIETARY_SUPPLEMENT

4.2 g/d (7 pills with 600 mg each)

Intervention Group; Placebo Group

Eligibility Criteria

• Age: 55 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age: ≥55 and ≤80 years
• BMI: ≥25.0 and ≤39.9 kg/m2;
• normal plasma glucose (fasting plasma glucose \<100 mg/dl and plasma glucose 2 h after a 75 g glucose challenge \<140 mg/dl) for the control group and impaired fasting plasma glucose (≥100 mg/dl) or impaired glucose tolerance (plasma glucose 2 h after a 75 g glucose challenge ≥140 mg/dl) or both for the intervention groups

You may not qualify if:

• age: \<55 and \>80 years
• BMI: \<25.0 and \>39.9 kg/m2
• fasting plasma glucose ≥100 mg/dl or plasma glucose 2 h after a 75 g glucose challenge ≥140 mg/dl for the control group and normal plasma glucose (fasting plasma glucose \<100 mg/dl, plasma glucose at 2 h after 75 g glucose ingestion \<140 mg/dl) for the intervention groups
• treatment for T2D, except for metformin
• regular structured high-intensity exercise \>150 min total per week
• significant neurological or other organ system dysfunction (e.g., progressive neuromuscular disease, unstable angina, vasculitis, certain cardiopulmonary diseases, cancer that has been in remission for \<5 years, dementia, allergies to the dietary supplement) or significant ambulatory impairments (e.g., limb amputations, being wheelchair-bound)
• use of certain medications that are incompatible with the study procedures (e.g., certain anticoagulants) or could confound the study outcomes (e.g., anabolic steroids, metronidazole, etc) alcohol use disorder as defined by the NIAAA or use of controlled substances or smoking \>20 cigarettes per week
• regular consumption of fish oil supplements or \>2 servings of fatty fish per week
• x) prisoners, and persons who are unable to grant voluntary informed consent.

Sponsors & Collaborators

• University of Missouri-Columbia: lead

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Diabetic Neuropathies

Condition Hierarchy (Ancestors)

Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Bettina Mittendorfer

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: double-blind, randomized controlled trial in men and women
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Associate Dean for Research

Study Record Dates

• First Submitted: July 9, 2020
• First Posted: December 6, 2021
• Study Start: January 14, 2021
• Primary Completion: June 26, 2023
• Study Completion: June 26, 2023
• Last Updated: March 11, 2026

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)