NCT02034331

Brief Summary

Persons with spinal cord injury (SCI) are at an increased risk for metabolic disorders, including that of insulin resistance. As a result of neurological injury, they often have impaired mechanisms that regulate blood vessel function below the level of injury. Insulin, which facilitates the transport of glucose into muscle cells, is also capable of regulating skin blood flow, with insulin resistance reducing perfusion. Although beyond the scope of this proposal, the possibility exists that impaired microvascular skin blood flow responses due to insulin may further predispose to ischemia of the skin at pressure points of bony prominence. This perturbed cutaneous vascular response may place persons with SCI at risk for the development and poor healing of pressure ulcers due to microvascular dysfunction secondary to neurologic and metabolic disorders. Primary Aim: To determine the association between systemic insulin sensitivity and insulin-mediated vasodilatation below the neurological level of injury. We hypothesize that individuals with systemic insulin sensitivity compared to those with insulin resistance will have greater insulin-mediated vasodilatation and an associated proportional increase in cutaneous blood perfusion. Thus, intact and appropriate endothelial-mediated regulation by insulin will be operative despite sub-lesional neurological impairment in insulin sensitive individuals with SCI. However, because of the absence of the SNS-mediated insulin action on the microvasculature (i.e., insulin-mediated sympathetic withdrawal), it is being hypothesized that the vasodilatory response to iontophoresis with insulin in insulin sensitive subjects with SCI will be less than that observed in neurologically intact controls with insulin sensitivity. Secondary Aim: To compare peak microvascular perfusion responses to endothelial-dependent vasodilatation by iontophoresis with acetylcholine to insulin. We hypothesize that the peak blood perfusion responses to iontophoresis with insulin will be comparable in magnitude to that of acetylcholine in individuals with greater systemic insulin sensitivity. This will be in contrast to individuals with systemic insulin resistance who will demonstrate a diminished response to iontophoresis with insulin when compared to that of acetylcholine. Because of SNS impairment, the peak vasodilatory response observed to these interventions will be lower in the group with SCI.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
68

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Dec 2012

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2012

Completed
1.1 years until next milestone

First Submitted

Initial submission to the registry

January 8, 2014

Completed
5 days until next milestone

First Posted

Study publicly available on registry

January 13, 2014

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2016

Completed
Last Updated

March 7, 2017

Status Verified

March 1, 2017

Enrollment Period

3 years

First QC Date

January 8, 2014

Last Update Submit

March 6, 2017

Conditions

Spinal Cord InjuryInsulin Resistance

Keywords

Insulin SensitivityMicrovascular permeabilitySympathetic nervous system

Outcome Measures

Primary Outcomes (1)

  • Cutaneous microvascular responses to insulin iontophoresis

    Iontophoresis with insulin will be performed in the arm and leg of individuals with spinal cord injury and able-bodied control subjects. The respective responses of the cutaneous microvascular beds to iontophoresis with insulin will be determined with considerations for the effects of sympathetic nervous system dysfunction as a result of spinal cord injury and systemic insulin sensitivity (as measured by an intravenous glucose tolerance test).

    Single time point

Study Arms (4)

Acetylcholine Iontophoresis

ACTIVE COMPARATOR

For acetylcholine iontophoresis, the anode electrode will contain 0.2 ml of 1% acetylcholine chloride; the cathode electrode will contain a medical grade adhesive for skin placement and last 20 minutes. Preparation, instrumentation and data collection for this intervention are the same as the insulin iontophoresis.

Drug: Acetylcholine Iontophoresis

Heat Application

ACTIVE COMPARATOR

For the provocation with heat, an insulated thermal heat pack (\~106°F) will be applied to the exposed arm or leg for 18 minutes. The thermal heat pack is comparable to what is routinely used as a heat therapy in conventional rehabilitation settings. LDF leads and temperature sensors will be placed in the previously specified locations to evaluate the changes.

Other: Heat application

Insulin Iontophoresis

EXPERIMENTAL

For insulin iontophoresis, the cathode electrode will contain 0.2 ml of liquid insulin. For preparation and instrumentation, the arms will be uncovered below the elbow; the participant's lower extremities will be uncovered below knee for leg evaluations. The laser Doppler flowmetry (LDF) lead will be placed bilaterally, 2 inches proximal to the lateral malleolus over the peroneus longus muscle. For arm evaluations, a lead will be placed (and secured with dual-sided transparent tape) bilaterally, 2 inches distal to the lateral epicondyle over the flexor carpi ulnaris muscle along the midline with the ulnar process. Baseline and peak cutaneous blood flow responses to application of insulin iontophoresis will be determined for each LDF lead during the evaluation.

Drug: Insulin iontophoresis

Placebo Iontophoresis

PLACEBO COMPARATOR

For placebo iontophoresis, the cathode electrode will contain 0.2 ml of preservative-free normal saline; the anode electrode will contain a medical grade adhesive for skin placement and last 20 minutes. Preparation, instrumentation and data collection for this intervention are the same as the insulin iontophoresis.

Drug: Placebo Iontophoresis

Interventions

Insulin iontophoresisDRUG

For insulin iontophoresis, the cathode electrode will contain 0.2 ml of liquid insulin. For preparation and instrumentation, the arms will be uncovered below the elbow; the participant's lower extremities will be uncovered below knee for leg evaluations. The laser Doppler flowmetry (LDF) lead will be placed bilaterally, 2 inches proximal to the lateral malleolus over the peroneus longus muscle. For arm evaluations, a lead will be placed (and secured with dual-sided transparent tape) bilaterally, 2 inches distal to the lateral epicondyle over the flexor carpi ulnaris muscle along the midline with the ulnar process. Baseline and peak cutaneous blood flow responses to application of insulin iontophoresis will be determined for each LDF lead during the evaluation.

Insulin Iontophoresis
Placebo IontophoresisDRUG

For placebo iontophoresis, the cathode electrode will contain 0.2 ml of preservative-free normal saline; the anode electrode will contain a medical grade adhesive for skin placement and last 20 minutes. Preparation, instrumentation and data collection for this intervention are the same as the insulin iontophoresis.

Placebo Iontophoresis
Acetylcholine IontophoresisDRUG

For acetylcholine iontophoresis, the anode electrode will contain 0.2 ml of 1% acetylcholine chloride; the cathode electrode will contain a medical grade adhesive for skin placement and last 20 minutes. Preparation, instrumentation and data collection for this intervention are the same as the insulin iontophoresis.

Acetylcholine Iontophoresis
Heat applicationOTHER

For the provocation with heat, an insulated thermal heat pack (\~106°F) will be applied to the exposed arm or leg for 18 minutes. The thermal heat pack is comparable to what is routinely used as a heat therapy in conventional rehabilitation settings. LDF leads and temperature sensors will be placed in the previously specified locations to evaluate the changes.

Heat Application

Eligibility Criteria

Age20 Years - 69 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Male or female, age 20 to 69;
  • Chronic (e.g., duration of injury at least 6 months), stable SCI (regardless of level of neurological lesion);
  • American Spinal Injury Association Impairment Scale (AIS) designation of A or B (reflects the level of somato-sensory impairment below the neurological level of injury: AIS A being complete sensory and motor lesion; AIS B being incomplete sensory and complete motor lesion);
  • Neurologically intact, age-matched control subjects
  • insulin-sensitive group: Si ≥ 2.5 min-1 ∙ mU-1 ∙ L x 104; and
  • insulin resistant group: Si \< 2.5 min-1 ∙ mU-1 ∙ L x 104

You may not qualify if:

  • Diminished mental capacity;
  • Inability or unwillingness of subject to provide informed consent;
  • Acute illness or infection;
  • Current pharmacological treatment for diabetes mellitus or insulin resistance with exogenous insulin (or its synthetic dialogues), insulin-sensitizing agents, or agents that alter pancreatic secretion of insulin;
  • Current pharmacological treatment with sympathomimetic agents demonstrating direct vascular actions or indirect implications (e.g., alpha-1 agonists, cholinesterase inhibitors, norepinephrine, calcium channel blockers, angiotensin converting enzymes);
  • Moderate to high dose glucocorticoid administrations (i.e., ≥ 40mg prednisone or equivalent steroid dose) within the past 3 months;
  • Atherosclerosis, congestive heart failure, or history of myocardial infarction;
  • Previous diagnosis of diabetes mellitus or insulin resistance; and
  • AIS designation of C, D or E (for SCI subjects only).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

James J. Peters VA Medical Center

The Bronx, New York, 10468, United States

Location

Related Publications (1)

  • La Fountaine MF, Rivera DR, Radulovic M, Bauman WA. The hemodynamic actions of insulin are blunted in the sublesional microvasculature of healthy persons with spinal cord injury. Am J Phys Med Rehabil. 2013 Feb;92(2):127-35. doi: 10.1097/PHM.0b013e31827d63ee.

    PMID: 23328885BACKGROUND

MeSH Terms

Conditions

Spinal Cord InjuriesInsulin Resistance

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesTrauma, Nervous SystemWounds and InjuriesHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • William A Bauman, MD

    James J. Peters VA Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
PARALLEL
Sponsor Type
FED
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director

Study Record Dates

First Submitted

January 8, 2014

First Posted

January 13, 2014

Study Start

December 1, 2012

Primary Completion

December 1, 2015

Study Completion

December 1, 2016

Last Updated

March 7, 2017

Record last verified: 2017-03

Locations

US(1)