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

Type 2 Diabetes Clinical Trial

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01238224
• Other study ID #: 2007-003921-25
• Status: Terminated
• Phase: Phase 1
• Start date: November 2009
• Est. completion date: November 2011

Study information

• Verified date: June 2015
• Source: Vastra Gotaland Region
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

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.

Description:

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 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 22
• Est. completion date: November 2011
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Postmenopausal state, defines as natural amenorrhea for at least 12 months.

2. Age; females 52-65 years, males: 40-65 years.

3. Type 2 diabetes based on fasting plasma glucose or 2-hr glucose after an OGTT.

4. Diabetes duration less than 5 years.

Exclusion Criteria:

1. 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%)

2. Patients on glitazones, insulin, beta-blockers, ACE-inhibitors and corticosteroids

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

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

Locations

Country	Name	City	State
Sweden	The Wallenberg Laboratory, Dept of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Bruna stråket 16,	Göteborg

Sponsors (1)

Lead Sponsor	Collaborator
Vastra Gotaland Region

Country where clinical trial is conducted

Sweden, 

References & Publications (1)

Jansson PA, Murdolo G, Sjögren L, Nyström B, Sjöstrand M, Strindberg L, Lönnroth P. Tadalafil increases muscle capillary recruitment and forearm glucose uptake in women with type 2 diabetes. Diabetologia. 2010 Oct;53(10):2205-8. doi: 10.1007/s00125-010-1819-4. Epub 2010 Jun 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Capillary recruitment, muscle glucose uptake and circulating glucose levels following a 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.	Five hours after a mixed meal
Secondary	Vascular function and circulating biomarkers.	Arterial stiffness as measured by pulse wave velocity and circulating concentrations of metabolic variables	Five hours after a mixed meal