Diabetes Mellitus, Type 2
Conditions
Keywords
endothelial dysfunction, vascular function, glycocalyx integrity assessment
Brief summary
The objective is to determine if neuraminidase inhibition with zanamivir is efficacious as a therapeutic strategy to restore endothelial function in T2D patients.
Detailed description
Twenty subjects will complete five days of treatment with zanamivir. Baseline measurements will be taken before the initiation of treatment, as well as after the conclusion of the treatment period (i.e., a total of two assessment visits per subject). Assessment visits will include: vitals (such as blood pressure, heart rate), fasting blood work for plasma neuraminidase activity, plasma sialic acid, plasma glucose and plasma insulin, brachial artery FMD, and glycocalyx integrity assessment via Glycocheck.
Interventions
DRUGZanamivir
5 days of treatment with 10mg zanamivir inhaler BID
Sponsors
University of Missouri-Columbia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single group design with 20 subjects
Eligibility
Sex/Gender
ALL
Age
45 Years to 64 Years
Healthy volunteers
No
Inclusion criteria
1. Men and women with a BMI of 25-39 kg/m2 2. Ages 45-64 years at randomization. 3. Diagnosis of T2D classified based on physician diagnosis. 4. No vulnerable populations (e.g., prisoners, pregnant, children) will be enrolled.
Exclusion criteria
1. Cardiovascular disease including myocardial infraction, heart failure, coronary artery disease, stroke 2. History of chronic renal or hepatic disease 3. Active cancer 4. Autoimmune diseases 5. Immunosuppressant therapy 6. Hormone replacement therapy 7. Excessive alcohol consumption (\>14 drinks/week for men, \>7 drinks/week for women) 8. Current tobacco use 9. Pregnancy (Premenopausal women will be required to complete a urine pregnancy test before participation) 10. History of asthma or chronic obstructive pulmonary disease. 11. History of allergic reaction to lactose or milk proteins 12. Intranasal live attenuated influenza vaccine (LAIV) given within 2 weeks before zanamivir administration or a planned dose within 48 hours after zanamivir administration. Product insert states to avoid zanamivir administration with intranasal live attenuated influenza vaccine (LAIV).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Glycocalyx Integrity-Perfused Boundary Region | Day 0 and Day 5 | Glycocalyx integrity will be assessed non-invasively using the GlycoCheck. The Glycocheck video microscope instrument will be placed under the subject's tongue to assess red blood cell penetration of the glycocalyx lining. PBR (perfused boundary region) is a measure of distance (mcm) that red blood cells penetrate into the glycocalyx. An increase in PBR in indicative of lower glycocalyx integrity. Outcomes are reported as a change in PBR from Day 0 to Day 5. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zanamivir Treatment Study participants will receive 5 days of treatment with a zanamivir inhaler.
Zanamivir: 5 days of treatment with 10mg zanamivir inhaler BID | 14 |
| Total | 14 |
Baseline characteristics
| Characteristic | Zanamivir Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 53 years STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 14 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 4 / 14 |
| serious Total, serious adverse events | 0 / 14 |
Outcome results
Primary
Change in Glycocalyx Integrity-Perfused Boundary Region
Glycocalyx integrity will be assessed non-invasively using the GlycoCheck. The Glycocheck video microscope instrument will be placed under the subject's tongue to assess red blood cell penetration of the glycocalyx lining. PBR (perfused boundary region) is a measure of distance (mcm) that red blood cells penetrate into the glycocalyx. An increase in PBR in indicative of lower glycocalyx integrity. Outcomes are reported as a change in PBR from Day 0 to Day 5.
Time frame: Day 0 and Day 5
Population: participants that completed full study intervention with baseline and day 5 assessment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zanamivir Treatment | Change in Glycocalyx Integrity-Perfused Boundary Region | -0.0057 micrometers (mcm) | Standard Error 0.11 |