Effects of PDE-5 Inhibition on Postprandial Hyperglycemia in Type 2 Diabetes

Sponsor

Vastra Gotaland Region (Other)

Overall Status

Terminated

CT.gov ID

NCT01238224

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

An increase of blood flow and capillary permeability decrease the impact of an endothelial barrier for glucose and insulin allowing them to reach their target cells in peripheral insulin sensitive organ in the human body. It is well known that insulin-resistant type 2 diabetes patients have an impaired blood flow in skeletal muscle and it is therefore important to elucidate means to reverse this metabolic defect.

The aim of this study is to test the hypothesis that tadalafil, compared to placebo, increases muscle glucose uptake and lowers blood glucose following a mixed meal served to type 2 diabetes patients.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Drug: Tadalafil	Phase 1

Detailed Description

The investigators have in a recently published study in type 2 diabetes patients used a drug against erectile dysfunction, the PDE-5 inhibitor tadalafil, with known effects on several vascular territories, to increase muscle blood flow in type 2 diabetes patients who were studied after fasting overnight. In fact, the investigators observed that tadalafil compared to placebo increased glucose uptake in muscle in parallel with an augmented capillary recruitment in muscle. This was the first publication to show that the pharmacological principle to inhibit the enzyme phosphodiesterase-5 (PDE-5) may mediate an increased muscle glucose uptake and, hence, may be a novel strategy to lower blood glucose in type 2 diabetes patients.

Study Design

Study Type:

Interventional

Actual Enrollment :

22 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

The Effect of Selective PDE-5 Inhibition on Capillary Recruitment, Glucose Uptake and Endothelial Function Following a Mixed Meal in Patients With Type 2 Diabetes Patients.

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Nov 1, 2011

Actual Study Completion Date :

Nov 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo A single dose of placebo is administered 30 min before a mixed meal.	Drug: Tadalafil This is an acute study. Tadalafil 20 mg administered prior to a meal Other Names: Cialis
Active Comparator: Tadalafil A single dose of tadalafil 20 mg is administered 30 min before a mixed meal.	Drug: Tadalafil This is an acute study. Tadalafil 20 mg administered prior to a meal Other Names: Cialis

Arm

Intervention/Treatment

Placebo Comparator: Placebo

A single dose of placebo is administered 30 min before a mixed meal.

Drug: Tadalafil

This is an acute study. Tadalafil 20 mg administered prior to a meal

Other Names:

Cialis

Active Comparator: Tadalafil

A single dose of tadalafil 20 mg is administered 30 min before a mixed meal.

Drug: Tadalafil

This is an acute study. Tadalafil 20 mg administered prior to a meal

Other Names:

Cialis

Outcome Measures

Primary Outcome Measures

Capillary recruitment, muscle glucose uptake and circulating glucose levels following a meal [Five hours after a mixed meal]
Capillary recruitment and glucose uptake in forearm muscle as well as circulating glucose levels following acute administration of tadalafil or placebo in type 2 diabetes patients.

Secondary Outcome Measures

Vascular function and circulating biomarkers. [Five hours after a mixed meal]
Arterial stiffness as measured by pulse wave velocity and circulating concentrations of metabolic variables

Eligibility Criteria

Criteria

Ages Eligible for Study:

40 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Postmenopausal state, defines as natural amenorrhea for at least 12 months.
Age; females 52-65 years, males: 40-65 years.
Type 2 diabetes based on fasting plasma glucose or 2-hr glucose after an OGTT.
Diabetes duration less than 5 years.

Exclusion Criteria:

Patients with concurrent use of nitrates or NO donors, history of heart or cerebrovascular disease, cardiac failure (stages NYHA II-IV), uncontrolled hypertension (> 160/100 mm Hg), significant diabetic complications, and inadequate glycemic control (HbA1c > 7%, ref value 3.5-5.3%)
Patients on glitazones, insulin, beta-blockers, ACE-inhibitors and corticosteroids

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Wallenberg Laboratory, Dept of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Bruna stråket 16,	Göteborg		Sweden	SE 413 45

Sponsors and Collaborators

Vastra Gotaland Region

Investigators

Principal Investigator: Per-Anders Jansson, MD, PhD, Region of Västra Götaland, Sahlgrenska University Hospital/Sahlgrenska University at University of Göteborg, Dept of Molecular and Clinical Medicine, SE 413 45 Göteborg, Sweden