Study to Determine How Cialis Effects the Renal Function in Response to Volume Expansion in Preclinical Systolic Cardiomyopathy (Aim2)

NCT01970176 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: 11-004644HL76611-07P3
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the effect of 12 weeks of chronic PDEV inhibition with Tadalafil versus placebo on basal cardiorenal and humoral function and on the integrated cardiorenal and humoral response to acute sodium loading in subjects with preclinical systolic dysfunction (PSD) and renal (kidney) dysfunction.

Conditions

Cardiomyopathy; Renal Impairment

Outcome Measures

Primary Outcomes (1)

• Change in Urinary Sodium Excretion

  Change in total urinary sodium excretion as measured by MEq/min

  Baseline, 12 weeks

Secondary Outcomes (2)

• Change in Glomerular Filtration Rate (GFR)

  Baseline, 12 weeks

• Change in Urinary Cyclic Guanosine 3',5'-Monophosphate (cGMP) Hormone Excretion

  Baseline, 12 weeks

Study Arms (2)

Tadalafil

ACTIVE COMPARATOR

Subject will receive Tadalafil daily for a total of 12 weeks

Drug: Tadalafil

Placebo

PLACEBO COMPARATOR

Subject will receive Placebo daily for a total of 12 weeks

Drug: Placebo

Interventions

Tadalafil DRUG

Tadalafil 5 mg tablet. Daily. Tadalafil dose varies from 5 mg to 20 mg for 12 weeks. If blood pressure is \>95 then subject dismissed from the Clinical Research Unit (CRU) on 2 (5 mg) tabs of tadalafil or placebo. If blood pressure is between 90 - 95 mmHg systolic, then dismiss on 1 (5 mg) tab of Tadalafil. At 2 weeks (± 5 days) if blood pressure is\> 100 than add 1 (5 mg) tab of Tadalafil to make a total of 3 (5mg) tabs of Tadalafil. At 4 weeks(± 5 days) if blood pressure is \> 100 add 1 (5 mg) tab to make a total of 4 (5 mg) tablets of Tadalafil.

Also known as: Tadalafil 5mg tablet

Tadalafil

Placebo DRUG

Placebo tablet. Daily. Placebo tablets made to match appearance of 5mg Tadalafil tablets. Placebo dose varies from 5 mg to 20 mg (1 to 4 tablets) for 12 weeks. If blood pressure is \>95 then subject dismissed from CRU on 2 tabs of placebo. If blood pressure is between 90 - 95 mmHg systolic, then dismiss on 1 (5 mg) tablet of placebo. At 2 weeks (± 5 days) if blood pressure is\> 100 than add 1 tab of placebo to make a total of 3 tablets of placebo. At 4 weeks(± 5 days) if blood pressure is \> 100 add 1 (5 mg) tab to make a total of 4 tablets of placebo.

Also known as: Placebo tablet

Placebo

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A total of 39 patients with PSD as defined by an ejection fraction of less than 40%, no clinical signs or symptoms of congestive heart failure, a minimal distance on 6-minute walk of equal or \>450 meters will be recruited and calculated creatinine clearance of equal or less than 90 ml/min and greater than 30 ml/min, using the (MDRD-measurement of renal dysfunction, formula) assessed within the past 24 months. If the subject is not able to walk 450 meters due to pain in hips and knees and not fatigue or shortness of breath than they will still qualify for the protocol.

You may not qualify if:

• Current or anticipated future need for nitrate therapy
• Systolic blood pressure \< 90 mmHg or \> 180 mm Hg
• Diastolic blood pressure \< 40 mmHg or \> 100 mmHg
• Patients taking alpha antagonists or cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, erythromycin, saquinavir, cimetidine or serum proteases inhibitors for HIV) who cannot be taken off these medications for the duration of the study.
• Patients taking the following selective alpha blockers and who are unable to stop for the duration of the study;
• Alfuzosin
• Prazosin
• Doxazosin
• Tamsulosin
• Terazosin
• Silodosin
• Patients with retinitis pigmentosa, previous diagnosis of nonischemic optic neuropathy, untreated proliferative retinopathy or unexplained visual disturbance
• Patients with sickle cell anemia, multiple myeloma, leukemia or penile deformities placing them at risk for priapism (angulation, cavernosal fibrosis or Peyronie's disease)
• Patients with an allergy to iodine.
• Patients on PDEV inhibition for pulmonary hypertension

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55902, United States

Location

Related Publications (1)

• Hubers SA, Wan SH, Adel FW, Benike SL, Burnett JC Jr, Scott C, Chen HH. Cardiorenal Effects of Long-Term Phosphodiesterase V Inhibition in Pre-Heart Failure. J Am Heart Assoc. 2022 Jan 18;11(2):e022126. doi: 10.1161/JAHA.121.022126. Epub 2022 Jan 8.

  PMID: 35001638 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Cardiomyopathies; Renal Insufficiency

Interventions

Tadalafil; Tablets

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Carbolines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indole Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Horng H. Chen, M.D.
• Organization: Mayo Clinic

chen.horng@mayo.edu

507-284-8896

Study Officials

• Horng H Chen, MD

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Professor of Medicine

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 25, 2013
• Study Start: January 9, 2014
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: June 11, 2021
• Results First Posted: July 17, 2020

Record last verified: 2021-06

Locations

US (1)