Skin Blood Flow Response to Insulin Iontophoresis in Pressure Ulcers of SCI

NCT02585765 | Withdrawn Phase 2 FDA Drug

• 1 other identifier: LAF-15-040
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Pressure ulcers (PU) are skin breakdowns that often form after blood flow in the skin is reduced from prolonged and repeated exposure to externally applied forces. As many as 85% of individuals with a spinal cord injury (SCI) report the occurrence of at least 1 PU since being injured. Despite the increasing attention and emphasis on prevention, PUs still represent a major health risk for persons with SCI. Among the numerous potential physical risk factors identified for the development of a PU were several conditions that have a significant negative effect on skin blood flow. In addition, improper management of blood sugar is a major risk factor for PU development and it impedes healing. It would appear that hormones (i.e., chemical signals in the blood) associated with how the body uses sugar that target the blood vessels may play an important role in the development and formation of a PU. In persons with SCI, skin blood flow responses to insulin (i.e., a hormone that helps the body use sugar and also relaxes the blood vessels allowing blood flow to increase) in the lower extremity were shown to be much lower than healthy individuals. The proposed study in up to 30 individuals with chronic SCI and a difficult-to-heal pelvic region PU has 2 phases: (1) a 4-week "observation" phase \[if the PU does not heal appropriately (determined by digital photos and software computation), and the subject is found to be insulin resistant then they will progress to the next phase of the study\] and (2) an 8-week "treatment" phase. All participants will continue to receive the standard wound care throughout the observation and treatment phases. If the surface area of the PU does not decrease by more than 30% during the 4-week observation phase, the participant will be eligible to enter the 8-week treatment phase, in which they will be randomly assigned to receive active drug (e.g., pioglitazone) or placebo. The participants will have four study visits in which the following will be acquired: digital image of the wound to monitor wound surface area, skin blood flow measurements of the peri-wound area, and blood tests to monitor liver function, kidney function, blood sugar (hemoglobin A1C, insulin, glucose), nutritional status (albumin and pre-albumin), a complete blood count with differential, and makers of inflammation. Weekly monitoring of symptoms and participant experiences will be closely monitored.

Conditions

Spinal Cord Injury; Pressure Ulcers

Outcome Measures

Primary Outcomes (1)

• Skin Perfusion Response to Insulin Administered by Iontophoresis to the Cutaneous Peri-Wound region of a Chronic Region Pressure Ulcer before and after treatment with Pioglitazone

  To determine the perfusion response to insulin administered by iontophoresis to the cutaneous peri-wound region of a chronic pelvic region pressure ulcer before and after treatment with pioglitazone (30 mg/d x 8 weeks).

  Before and After 8 Week Treatment with Pioglitazone

Secondary Outcomes (1)

• Association between the therapeutic effects of pioglitazone on the homeostatic model assessment of insulin resistance (HOMA-IR) and cutaneous peri-wound perfusion response to transdermal insulin administration.

  Before and After 8 Week Treatment with Pioglitazone

Other Outcomes (1)

• Reliability of laser speckle contrast analysis imaging to detect meaningful interventional change in cutaneous peri-wound perfusion to pioglitazone treatment.

  Before and After 8 Week Treatment with Pioglitazone

Study Arms (2)

Pioglitazone

EXPERIMENTAL

Subjects will receive 8 weeks of daily pioglitazone (30mg/day).

Drug: Pioglitazone

Placebo

PLACEBO COMPARATOR

Subjects will receive 8 weeks of daily placebo capsules.

Drug: Placebo

Interventions

Pioglitazone DRUG

8 weeks of daily pioglitazone (30 mg/d).

Pioglitazone

Placebo DRUG

8 weeks of daily placebo capsules.

Placebo

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18 to 79;
• 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, B or C; and
• At least one Stage III or IV PU in the pelvic region (e.g., ischial, trochanteric, perineal, and sacral regions) that has not shown signs of healing for a period of at least 1 month.
• Hemoglobin A1C \<7.0%

You may not qualify if:

• Persons who are candidates for or elect to have reconstructive flap surgery of the PU;
• Hemoglobin A1C ≥7.0%
• Psychopathology (documentation in the medical record or history of self-abusive behavior specific to PU healing which may or may not include major or minor psychiatric illness (that may conflict with the study objectives;
• Previously diagnosed active malignant disease;
• Suspicion of skin cancer at the PU site (i.e., clinical evaluation is currently on-going);
• Life expectancy less than 12 months;
• Nephrosis, hemodialysis or chronic ambulatory peritoneal dialysis therapy;
• Acute illness or systemic infection (including MRSA);
• 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., ≥ 40 mg prednisone or equivalent steroid dose) within the past 3 months;
• Atherosclerosis, congestive heart failure, or recent history of myocardial infarction (\<90 months);
• Previous diagnosis of diabetes mellitus or insulin resistance;
• Diminished mental capacity;
• Inability or unwillingness of subject to provide informed consent; or

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead

Study Sites (1)

James J. Peters VA Medical Center

The Bronx, New York, 10468, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Pressure Ulcer

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Health Science Specialist

Study Record Dates

• First Submitted: October 22, 2015
• First Posted: October 23, 2015
• Study Start: February 1, 2017
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: August 8, 2018

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)