Effects on Insulin Resistance With Tadalafil in Type 2 Diabetes - a Double-blind, Placebo-controlled Crossover Study

NCT ID: NCT02601989

Last Updated: 2020-02-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-11-30
• Study Completion Date: 2019-01-31

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.

Conditions

Diabetes Mellitus, Type 2

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Tadalafil

Per oral intake of tadalafil 20 mg o.d. for six weeks

Group Type: EXPERIMENTAL

Tadalafil

Intervention Type: DRUG

Placebo

Per oral intake of placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Per oral intake of placebo for six weeks

Interventions

Tadalafil

Intervention Type: DRUG

Placebo

Per oral intake of placebo for six weeks

Intervention Type: DRUG

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.

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vastra Gotaland Region

OTHER_GOV

Sponsor Role: collaborator

Göteborg University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Per-Anders Jansson, MD

Role: PRINCIPAL_INVESTIGATOR

Göteborg University

Locations

Sahlgrenska University Hospital

Gothenburg, , Sweden

Countries

Sweden

References

Fryk E, Rodrigues Silva VR, Bauza-Thorbrugge M, Schmelz M, Gan LM, Strindberg L, Jansson PA. Feasibility of high-dose tadalafil and effects on insulin resistance in well-controlled patients with type 2 diabetes (MAKROTAD): a single-centre, double-blind, randomised, placebo-controlled, cross-over phase 2 trial. EClinicalMedicine. 2023 May 4;59:101985. doi: 10.1016/j.eclinm.2023.101985. eCollection 2023 May.

Reference Type: DERIVED

PMID: 37256099 (View on PubMed)

Other Identifiers

2015-000573-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2015-09-14

Identifier Type: -

Identifier Source: org_study_id