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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified November 2010 by Vastra Gotaland Region.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Vastra Gotaland Region
ClinicalTrials.gov Identifier:
NCT01238224
First received: October 6, 2010
Last updated: November 9, 2010
Last verified: November 2010
  Purpose

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.


Condition Intervention
Type 2 Diabetes
Drug: Tadalafil

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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.

Resource links provided by NLM:


Further study details as provided by Vastra Gotaland Region:

Primary Outcome Measures:
  • Capillary recruitment, muscle glucose uptake and circulating glucose levels following a meal [ Time Frame: Five hours after a mixed meal ] [ Designated as safety issue: No ]
    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. [ Time Frame: Five hours after a mixed meal ] [ Designated as safety issue: No ]
    Arterial stiffness as measured by pulse wave velocity and circulating concentrations of metabolic variables


Estimated Enrollment: 40
Study Start Date: November 2009
Estimated Study Completion Date: December 2011
Estimated Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Tadalafil
    This is an acute study. Tadalafil 20 mg administered prior to a meal
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

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 3 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 > 6.5%, ref value 3.5-5.3%)
  2. Patients on glitazones, insulin, beta-blockers, ACE-inhibitors, angiotensin II subtype 1 receptor blockers and corticosteroids
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01238224

Contacts
Contact: Per-Anders Jansson, MD, PhD +46 31 3421000 per-anders.jansson@medic.gu.se

Locations
Sweden
The Wallenberg Laboratory, Dept of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Bruna stråket 16, Recruiting
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
  More Information

Publications:
Responsible Party: Per-Anders Jansson, MD, PhD, Region of Västra Götaland, Sahlgrenska University Hospital & Sahlgrenska Academy at Göteborg University
ClinicalTrials.gov Identifier: NCT01238224     History of Changes
Other Study ID Numbers: 2007-003921-25
Study First Received: October 6, 2010
Last Updated: November 9, 2010
Health Authority: Sweden: The National Board of Health and Welfare

Keywords provided by Vastra Gotaland Region:
Insulin resistance
Phosphodiesterase-5 inhibition
Microdialysis
Type 2 diabetes
Endothelial dysfunction
Oral hypoglycaemic agents

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Hyperglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Tadalafil
Vasodilator Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Phosphodiesterase 5 Inhibitors
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 21, 2014