Trial Outcomes & Findings for CD36 in Nutrient Delivery and Its Dysfunction (NCT NCT03012386)

Last Updated: 2022-11-30

Results Overview

Insulin induces microvascular recruitment. Changes in MBV during Insulin infusion signifies insulin sensitivity. MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a hyperinsulinaemic euglycaemic (HIE) clamp (insulin infusion rate up to 80 mU/m2.min-1 ). In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

26 participants

Primary outcome timeframe

Baseline to end of procedure (approximately 180 minutes)

Results posted on

2022-11-30

Participant Flow

35 subjects were screened, 9 were excluded for not meeting the inclusion criteria

21 subjects completed the study

Participant milestones

Participant milestones
Measure	Sildenafil Citrate in G Allele Carriers Sildenafil citrate 20 mg three times a day Sildenafil Citrate: phosphodiesterase 5 inhibitor	Sildenafil Citrate in Non Carriers of G Allele Sildenafil citrate 20 mg three times a day Sildenafil Citrate: phosphodiesterase 5 inhibitor
Overall Study STARTED	8	18
Overall Study COMPLETED	8	13
Overall Study NOT COMPLETED	0	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

CD36 in Nutrient Delivery and Its Dysfunction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sildenafil Citrate in G Allele Carriers n=8 Participants Sildenafil citrate 20 mg three times a day Sildenafil Citrate: phosphodiesterase 5 inhibitor	Sildenafil Citrate in Non Carriers of G Allele n=18 Participants Sildenafil citrate 20 mg three times a day Sildenafil Citrate: phosphodiesterase 5 inhibitor	Total n=26 Participants Total of all reporting groups
Age, Customized Age	42 years STANDARD_DEVIATION 7.4 • n=5 Participants	33.66 years STANDARD_DEVIATION 7.4 • n=7 Participants	37.83 years STANDARD_DEVIATION 7.4 • n=5 Participants
Sex: Female, Male Gender · Female	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Sex: Female, Male Gender · Male	3 Participants n=5 Participants	14 Participants n=7 Participants	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=5 Participants	18 Participants n=7 Participants	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Height	169 centimeters STANDARD_DEVIATION 9.3 • n=5 Participants	166.22 centimeters STANDARD_DEVIATION 8.72 • n=7 Participants	167.61 centimeters STANDARD_DEVIATION 9.3 • n=5 Participants
Weight	79 Kg STANDARD_DEVIATION 8.34 • n=5 Participants	92.95 Kg STANDARD_DEVIATION 14.8 • n=7 Participants	85.9 Kg STANDARD_DEVIATION 14.8 • n=5 Participants
BMI	27.7 kg/m^2 STANDARD_DEVIATION 2.8 • n=5 Participants	33.53 kg/m^2 STANDARD_DEVIATION 3.9 • n=7 Participants	30.615 kg/m^2 STANDARD_DEVIATION 3.9 • n=5 Participants
Glucose	81 mg/dl STANDARD_DEVIATION 10.0 • n=5 Participants	83.5 mg/dl STANDARD_DEVIATION 17.7 • n=7 Participants	82.25 mg/dl STANDARD_DEVIATION 17.7 • n=5 Participants
Total cholesterol	180 mg/dl STANDARD_DEVIATION 37.1 • n=5 Participants	171.66 mg/dl STANDARD_DEVIATION 29.48 • n=7 Participants	175.83 mg/dl STANDARD_DEVIATION 33.2 • n=5 Participants
HDL	51 mg/dl STANDARD_DEVIATION 13.8 • n=5 Participants	53.38 mg/dl STANDARD_DEVIATION 13.3 • n=7 Participants	52.1 mg/dl STANDARD_DEVIATION 13.6 • n=5 Participants
LDL	106 mg/dl STANDARD_DEVIATION 36.2 • n=5 Participants	100.88 mg/dl STANDARD_DEVIATION 28.25 • n=7 Participants	103.44 mg/dl STANDARD_DEVIATION 32.2 • n=5 Participants
Triglycerides	116.37 mg/dl STANDARD_DEVIATION 73.85 • n=5 Participants	87.11 mg/dl STANDARD_DEVIATION 47.42 • n=7 Participants	101.74 mg/dl STANDARD_DEVIATION 60.6 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline to end of procedure (approximately 180 minutes)

Outcome measures

Outcome measures
Measure	G Allele Carriers n=8 Participants The participants were divided into two groups based on the CD36 rs3211938 genotype. subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in reduction of CD36 levels	Non Carriers of G Allele n=13 Participants The participants were divided into two groups based on the CD36 rs3211938 genotype.
Change in Microvascular Blood Volume (MBV) During Insulin Infusion	13.16 ml/kg Standard Deviation 3.369	11.3 ml/kg Standard Deviation 1.37

PRIMARY outcome

Timeframe: Baseline to 4 weeks

Chronic treatment with sildenafil increases vascularity and muscle glucose uptake. Changes in MBV during Insulin infusion signifies insulin sensitivity . Insulin sensitivity was tested after 4 weeks of treatment with Sildenafil in both groups. Subjects receive IV infusion of 20% Intralipid (45ml/h) and heparin (200 units/hr). MBV is measured in the forearm brachioradialis muscle with contrast enhanced ultrasonography during minutes 120-150 of a HIE clamp (insulin infusion rate up to 80 mU/m2.min-1 ) In the last 30 minutes, L-arginine was infused (10 mg/kg/min for 30 minutes) and ultrasound measurements were repeated upon infusion completion (approximately minute 180).

Outcome measures

Outcome measures
Measure	G Allele Carriers n=8 Participants The participants were divided into two groups based on the CD36 rs3211938 genotype. subjects carrying the G-allele of CD36 coding SNP rs3211938 that results in reduction of CD36 levels	Non Carriers of G Allele n=13 Participants The participants were divided into two groups based on the CD36 rs3211938 genotype.
Change in Microvascular Blood Volume (MBV) During Insulin Infusion After 4 Weeks of Sildenafil Treatment in Both Groups	12.93 ml/kg Standard Deviation 2.31	8.4 ml/kg Standard Deviation 0.63

Adverse Events

Sildenafil Citrate

Serious events: 2 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Sildenafil Citrate n=26 participants at risk Sildenafil citrate 20 mg three times a day Sildenafil Citrate in G allele carrier: chronic use of phosphodiesterase 5 inhibitor in G allele carrier Sildenafil Citrate in non G allele carrier: chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier
Pregnancy, puerperium and perinatal conditions Positive pregnancy test	3.8% 1/26 • Number of events 1 • 12 weeks
Infections and infestations Malaria	3.8% 1/26 • Number of events 1 • 12 weeks

Other adverse events

Other adverse events
Measure	Sildenafil Citrate n=26 participants at risk Sildenafil citrate 20 mg three times a day Sildenafil Citrate in G allele carrier: chronic use of phosphodiesterase 5 inhibitor in G allele carrier Sildenafil Citrate in non G allele carrier: chronic use of phosphodiesterase 5 inhibitor in Non G allele carrier
Skin and subcutaneous tissue disorders Rash and itchiness all over the body	7.7% 2/26 • 12 weeks
Respiratory, thoracic and mediastinal disorders Cough congestion	3.8% 1/26 • 12 weeks
Gastrointestinal disorders Diarrhea	3.8% 1/26 • 12 weeks
Infections and infestations Upset stomach / stomach virus	3.8% 1/26 • 12 weeks
Psychiatric disorders Burst of enerygy/ Irritability	3.8% 1/26 • 12 weeks
Nervous system disorders Headaches	11.5% 3/26 • 12 weeks
Musculoskeletal and connective tissue disorders Low back pain/ Leg heaviness	11.5% 3/26 • 12 weeks

Additional Information

Cyndya Shibao MD

Vanderbilt University Medical Center

Phone: 6159364584

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place