Clinical trial NCT02034266: The Effect of Omega-3 Supplementation on Nerve Structure and Function in Type 1 Diabetes
Official title: Phase 2 Study of the Effects of Omega-3 Fatty Acid Supplementation on Nerve Structure and Function in Type 1 Diabetes Mellitus - A Clinical Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type one diabetes
nerve damage
neuropathy
omega-3 fatty acid
supplementation
nutrition
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
Collaborators: name: Canadian Diabetes Association
First posted: 2014-01-13
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label study with no placebo.
Primary purpose: PREVENTION

Brief summary: Nerves are made of different fats including omega-3s and omega-6s; however, dietary intakes of omega-6s are very high and omega-3 intakes are very low. We hypothesize that omega-3 supplementation will stop diabetes related changes in cornea nerve structure in patients with type 1 diabetes to stop the development of nerve injury associated with future risk of neuropathy, and reflect changes in the degree of nerve injury over time. As such, we anticipate that patients in the study will maintain Corneal Nerve Fiber Length (CNFL), the primary outcome measure.

Detailed description: This study will test the use of an omega-3 supplement as a potential way to stop nerve damage that has been observed in individuals with type 1 diabetes Nerves supply signals to all structures in the body and take signals back to the spinal cord and brain. Both small and large nerve fibres can be affected in disease states, such as diabetes. Since defects of small nerve fibre activity have important consequences (painful symptoms, erectile dysfunction, cardiac rhythm disturbances, bladder and gastrointestinal dysfunction), it is important to determine new ways to maintain their function to help individuals maintain a high quality of life.

Until now, researchers have only tested the effect of omega-3 supplementation in animals with diabetes and have found this nutrient to lessen nerve damage while maintaining the function of nerves. However, there has not been any research on the use of omega-3s on nerve structure and function in humans with type 1 diabetes.

Current standard of care for type 1 diabetes is to manage glycemic control and any painful symptoms through medication. The use of omega-3 supplements for prevent or limit nerve damage in diabetes is not within the current standard of care. In this study omega-3 supplementation is experimental and has been approved by Health Canada for use in this study.

Eligibility criteria: Inclusion Criteria:

A. Patients of any gender or race aged 18 or above B. Type 1 diabetes mellitus as defined by the 2008 Canadian Diabetes Association C. Toronto Clinical Neuropathy Score ≥1 D. Ability to understand and cooperate with study procedures

Exclusion Criteria:

A. Current eye infection or damage of cornea B. Severe movement disorder C. History of allergy to proparacaine (the ocular topical anaesthetic used for the corneal confocal microscopy exam) D. Inability to sit and lie supine comfortably for 45-60 minutes E. Major medical or psychiatric illness that would preclude successful participation in the study F. Unwillingness to sign informed consent. G. Confirmed neuropathy secondary to non-diabetic causes (examples include polyneuropathy owing to alcohol abuse, B12 deficiency, folate deficiency, chronic renal failure, hypothyroidism, or neurotoxic drug use such as chemotherapy).

H. Current or previous regular (\>3 times per week) consumption of omega-3 supplements within the past month I. Consistently consuming fish \>2 times per week in the past month J. Performing regular exercise \>3 times per week in the past 3 months

Primary outcomes:
measure: Change in corneal nerve fibre length
timeFrame: Baseline and 12 months
Secondary outcomes:
measure: Nerve Conduction Studies
timeFrame: Baseline and 12 months
measure: Corneal Nerve Fibre Length
timeFrame: 4 months and 8 months
measure: Laser Doppler Imaging Flare (LDI Flare) sympathetic skin response
timeFrame: Baseline and 12 months
measure: Vibration Perception Threshold
timeFrame: Baseline and 12 months
measure: Cooling Detection Threshold Testing
timeFrame: Baseline and 12 months
measure: Omega-3 status
timeFrame: Baseline, 4, 8 and 12 months
measure: Heart Rate Variability
timeFrame: Baseline and 12 months
measure: R-R interval
timeFrame: Baseline and 12 months
Other outcomes:
measure: Glycated hemoglobin A1c
timeFrame: Baseline and 12 months
measure: Serum lipids
timeFrame: Baseline and 12 months
measure: Thyroid stimulating hormone
timeFrame: Baseline and 12 months
measure: Creatinine
timeFrame: Baseline and 12 months
measure: Vitamin B12
timeFrame: Baseline and 12 months
measure: Serum Folate
timeFrame: Baseline and 12 months
measure: Uric acid
timeFrame: Baseline and 12 months
measure: Urinary albumin excretion
timeFrame: Baseline and 12 months
measure: Serum protein electrophoresis
timeFrame: Baseline and 12 months
measure: Serum C-reactive protein
timeFrame: Baseline and 12 months
measure: Serum fatty acid profile
timeFrame: Baseline and 12 months
Locations:
city: Toronto
country: Canada
facility: University Health Network, Division of Neurology, Toronto General Hospital
state: Ontario
Study officials:
affiliation: University Health Network, Toronto
name: Vera Bril, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Lewis EJH, Perkins BA, Lovblom LE, Bazinet RP, Wolever TMS, Bril V. Effect of omega-3 supplementation on neuropathy in type 1 diabetes: A 12-month pilot trial. Neurology. 2017 Jun 13;88(24):2294-2301. doi: 10.1212/WNL.0000000000004033. Epub 2017 May 17.