Clinical trial NCT02601989: Effects on Insulin Resistance With Tadalafil in Type 2 Diabetes - a Double-blind, Placebo-controlled Crossover Study
Official title: Effects on Insulin Resistance With the Phosphodiesterase-5 Inhibitor Tadalafil in Type 2 Diabetes - a Double-blind, Placebo-controlled Crossover Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetes Mellitus, Type 2
Lead sponsor: Göteborg University
Sponsor class: OTHER
Collaborators: name: Vastra Gotaland Region
First posted: 2015-11-11
Enrollment: 23
Sex: ALL
Minimum age (years): 40
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: SUPPORTIVE_CARE

Brief summary: The aim is to continue our program on PDE5 inhibition by evaluating effects on insulin resistance, including glucose metabolism and subclinical inflammation, after a 6-week administration of tadalafil in T2D patients. The primary objective is to study the effect of tadalafil compared with placebo on insulin sensitivity during a euglycemic hyperinsulinemic clamp.

This is a double-blind, placebo-controlled crossover study with one study site. Twenty-five T2D patients will be recruited and randomized to per oral intake of tadalafil 20 mg o.d. for six weeks and after a wash-out period of eight weeks intake of placebo for another six weeks, or vice versa. At the end of each 6 week treatment period a glucose clamp, subcutaneous needle biopsies as well as muscle and subcutaneous microdialysis will be performed. Endothelial function tests and arginin stimulation of insulin secretion tests will be performed after 3 weeks in each treatment arm.


Eligibility criteria: Inclusion Criteria:

1. T2D patient, previously diagnosed by fasting or 2-hr OGTT plasma glucose levels
2. Age females: 55-70 yrs (post-menopausal state defined as natural amenorrhea for at least 12 months); Age males: 40-70 yrs
3. BMI: 27-40 kg/m2
4. HbA1c \< 60 mmol/mol
5. Type 2 diabetes duration \> 3 months and \< 10 yrs
6. Understand and speak Swedish

Exclusion Criteria:

1. Diabetes treatment with glitazones, GLP-1 analogues or DPP-IV inhibitors
2. Anti-hypertensive therapy with beta-blockers, ACE-inhibitors and/or angiotensin-II receptor blockers
3. Significant microvascular complications e.g. nephropathy (GFR\<60), proliferative retinopathy and symptomatic neuropathy e.g. postural hypotension
4. Previous significant vascular disease including angina pectoris and myocardial infarction, cerebral artery disease e.g. history of transient ischemic attacks and peripheral artery disease with no palpable pulses
5. Smoking \> 10 cig/day and/or smokeless tobacco \> one can per 2 days
6. Concurrent use of nitrates or NO donors, or an apparent risk that there may be a need of such medication
7. Cardiac failure (stages NYHA II-IV)
8. Uncontrolled hypertension \> 170/105 mm Hg
9. Apparent ECG-pathology indicating current or previous myocardial ischemia;
10. Males with erectile dysfunction
11. Hemophilia or a history of bruises or hepatic failure (\> 2-fold increase upper limit normal values of ASAT/ALAT)
12. Hypotension
13. Treatment with doxazosin
14. Anything in the contact with the patient that makes the doctor to believe that he/she will be uncompliant to the protocol.

Primary outcomes:
measure: insulin sensitivity
timeFrame: 6 week treatment with drug or placebo
Secondary outcomes:
measure: Mean glucose (HbA1c, mmol/mol) in blood
timeFrame: Up to 6 weeks after start of treatment.
measure: Fasting plasma glucose levels (mmol/l)
timeFrame: Up to 6 weeks after start of treatment.
measure: Arginine-induced insulin secretion (area under curve, AUC, mU/l/min) in blood
timeFrame: 3 weeks after start of treatment.
measure: Levels interstitial insulin
timeFrame: Up to 6 weeks after start of treatment.
measure: Lactate concentrations in insulin sensitive tissues
timeFrame: Up to 6 weeks after start of treatment.
measure: Levels of inflammatory markers in blood
timeFrame: Up to 6 weeks after start of treatment.
measure: Endothelial function in peripheral arteries measured with EndoPAT, measured as difference in reactive hyperemia
timeFrame: 3 weeks after start of treatment.
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Göteborg University
name: Per-Anders Jansson, MD
role: PRINCIPAL_INVESTIGATOR
References: