Clinical trial NCT01238224: Effects of PDE-5 Inhibition on Postprandial Hyperglycemia in Type 2 Diabetes
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Type 2 Diabetes
Keywords: Insulin resistance
Phosphodiesterase-5 inhibition
Microdialysis
Type 2 diabetes
Endothelial dysfunction
Oral hypoglycaemic agents
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2010-11-10
Enrollment: 22
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Capillary recruitment, muscle glucose uptake and circulating glucose levels following a meal
timeFrame: Five hours after a mixed meal
Secondary outcomes:
measure: Vascular function and circulating biomarkers.
timeFrame: Five hours after a mixed meal
Other outcomes:
Locations:
city: Göteborg
country: Sweden
facility: The Wallenberg Laboratory, Dept of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Bruna stråket 16,
Study officials:
affiliation: Region of Västra Götaland, Sahlgrenska University Hospital/Sahlgrenska University at University of Göteborg, Dept of Molecular and Clinical Medicine, SE 413 45 Göteborg, Sweden
name: Per-Anders Jansson, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jansson PA, Murdolo G, Sjogren L, Nystrom B, Sjostrand M, Strindberg L, Lonnroth 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.