Trial Outcomes & Findings for A Trial of Tadalafil and Glycemic Traits (NCT NCT01444651)

NCT ID: NCT01444651

Last Updated: 2017-01-30

Results Overview

The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = \[fasting glucose \* fasting insulin\]/405

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 73 participants
• Primary outcome timeframe: Baseline and 3 months
• Results posted on: 2017-01-30

Participant Flow

111 participants screened, 38 excluded (34 did not meet eligibility criteria, 2 unable to obtain intravenous access, 2 withdrew consent)

Participant milestones

Measure	Tadalafil 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Overall Study STARTED	36	37
Overall Study COMPLETED	25	28
Overall Study NOT COMPLETED	11	9

Reasons for withdrawal

Measure	Tadalafil 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Overall Study Adverse Event	3	2
Overall Study Lost to Follow-up	5	5
Overall Study Non-fasting	2	1
Overall Study Missing data	1	1

Baseline Characteristics

A Trial of Tadalafil and Glycemic Traits

Baseline characteristics by cohort

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months	Total n=53 Participants Total of all reporting groups
Age, Continuous	33 years STANDARD_DEVIATION 9 • n=93 Participants	34 years STANDARD_DEVIATION 9 • n=4 Participants	33 years STANDARD_DEVIATION 9 • n=27 Participants
Gender Female	7 Participants n=93 Participants	13 Participants n=4 Participants	20 Participants n=27 Participants
Gender Male	18 Participants n=93 Participants	15 Participants n=4 Participants	33 Participants n=27 Participants
Region of Enrollment United States	25 participants n=93 Participants	28 participants n=4 Participants	53 participants n=27 Participants
Body mass index	38.7 kg/m^2 STANDARD_DEVIATION 6.8 • n=93 Participants	36.8 kg/m^2 STANDARD_DEVIATION 6.8 • n=4 Participants	37.7 kg/m^2 STANDARD_DEVIATION 6.8 • n=27 Participants
Fasting insulin	17 microunits/mL STANDARD_DEVIATION 10 • n=93 Participants	17 microunits/mL STANDARD_DEVIATION 16 • n=4 Participants	17 microunits/mL STANDARD_DEVIATION 13 • n=27 Participants

PRIMARY outcome

Timeframe: Baseline and 3 months

The primary endpoint is defined as the treatment group difference in the change in insulin resistance (baseline HOMA-IR minus 3-month HOMA-IR). HOMA-IR = [fasting glucose * fasting insulin]/405

Outcome measures

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR Baseline	3.57 mg*microunits/dL*mL Standard Deviation 2.86	3.84 mg*microunits/dL*mL Standard Deviation 3.80
Change in Insulin Resistance From Baseline to 3 Months, as Measured by HOMA-IR 3 months	3.81 mg*microunits/dL*mL Standard Deviation 5.14	5.06 mg*microunits/dL*mL Standard Deviation 3.95

SECONDARY outcome

Timeframe: Baseline and 3 months

The secondary endpoint is defined as the treatment group difference in the change in Matsuda Index (baseline minus 3-month). This index is a measure of insulin resistance derived from a frequently sampled oral glucose tolerance test, obtaining glucose and insulin levels in the fasting state, as well as 30, 60, 90, and 120 min after administration of oral glucose load. Matsuda index = 10,000/SQRT [fasting glucose*fasting insulin* (mean glucose from time 30, 60, 90, 120 min) * (mean insulin at time 30, 60, 90, and 120 min)]

Outcome measures

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index Baseline	3.60 unitless index Standard Deviation 2.54	3.51 unitless index Standard Deviation 2.15
Baseline to 3-month Change in Insulin Sensitivity, as Measured by the Matsuda Index 3 months	4.27 unitless index Standard Deviation 2.83	3.28 unitless index Standard Deviation 2.42

SECONDARY outcome

Timeframe: Baseline and 3 months

Endothelial function was measured using the reactive hyperemia index, acquired using EndoPAT device. Peripheral arterial tonometry probes were placed on both index fingers. After a 5 min equilibration period, a blood pressure cuff was inflated to 200 mmHg and kept inflated for 5 min. The cuff was then rapidly deflated and the reactive hyperemic response pulse volume recorded, where RHI = ratio of hyperemic finger pulse volume (post-cuff inflation / pre-cuff inflation) to control finger pulse volume (post-cuff inflation / pre-cuff inflation)

Outcome measures

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Baseline to 3-month Change in Endothelial Function Measured by EndoPAT Baseline	2.1 unitless index Standard Deviation 0.5	2.3 unitless index Standard Deviation 0.6
Baseline to 3-month Change in Endothelial Function Measured by EndoPAT 3-month	2.1 unitless index Standard Deviation 2.7	2.2 unitless index Standard Deviation 0.3

SECONDARY outcome

Timeframe: Baseline and 3 months

The secondary endpoint is defined as the treatment group difference in the change in insulinogenic index (baseline minus 3-month). This index is thought to reflect insulin secretion, and is derived from fasting and 30 min-post oral glucose tolerance testing glucose and insulin values. Insulinogenic index = [fasting insulin - insulin at time 30 min] / [fasting glucose - glucose at time 30 min]

Outcome measures

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Insulinogenic Index Baseline	0.39 unitless index Standard Deviation 8.04	2.17 unitless index Standard Deviation 2.06
Insulinogenic Index 3-month	2.62 unitless index Standard Deviation 3.03	1.04 unitless index Standard Deviation 2.32

SECONDARY outcome

Timeframe: Baseline and 3 months

The secondary endpoint is defined as the treatment group difference in the change in oral disposition index (baseline minus 3-month). This is thought to reflect a composite of both insulin resistance and secretion. Oral disposition index = insulinogenic index / fasting insulin

Outcome measures

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index Baseline	1.74 unitless index Standard Deviation 11.56	2.87 unitless index Standard Deviation 3.67
Baseline to 3 Month Change in Composite of Insulin Resistance and Sensitivity, as Measured by the Oral Disposition Index 3-month	4.48 unitless index Standard Deviation 4.62	0.58 unitless index Standard Deviation 5.21

SECONDARY outcome

Timeframe: Baseline and 3 months

Change in disposition index from baseline to 3 months. This index is a composite measure thought to reflect insulin resistance and secretion. Matsuda disposition index = [Matsuda sensitivity index * insulinogenic index]

Outcome measures

Measure	Tadalafil n=25 Participants 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=28 Participants Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Baseline to 3-month Change in Matsuda Disposition Index Baseline	2.23 unitless index Standard Deviation 24.19	6.67 unitless index Standard Deviation 9.45
Baseline to 3-month Change in Matsuda Disposition Index 3-month	9.22 unitless index Standard Deviation 8.51	0.19 unitless index Standard Deviation 18.42

Adverse Events

Tadalafil

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Tadalafil n=36 participants at risk 20 mg Tadalafil tablet taken by mouth once a day for 3 months Tadalafil: 20 mg Tadalafil taken once a day for 3 months	Placebo n=37 participants at risk Placebo tablet taken by mouth once a day for 3 months Placebo: Placebo tablet taken by mouth once a day for 3 months
Vascular disorders Headache	11.1% 4/36 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit	0.00% 0/37 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit
Vascular disorders Blurry vision and headache	0.00% 0/36 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit	2.7% 1/37 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit
Musculoskeletal and connective tissue disorders Back or leg pain	5.6% 2/36 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit	0.00% 0/37 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit
Musculoskeletal and connective tissue disorders Headache and back ache	2.8% 1/36 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit	0.00% 0/37 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit
Musculoskeletal and connective tissue disorders arm pain	0.00% 0/36 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit	2.7% 1/37 • Adverse events recorded during study duration (3 months) Adverse events ascertained at each follow-up visit

Additional Information

Dr. Jennifer Ho

Massachusetts General Hospital

Phone: 617-726-6411

Email: jho1@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place