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- Sperimentazione clinica NCT02819440
PDE5 Inhibition for Obesity-Related Cardiometabolic Dysfunction
Panoramica dello studio
Descrizione dettagliata
Obesity is a risk factor for nearly all cardiovascular (CV) disease including coronary artery disease, hypertension, and heart failure. Increased CV risk in obese individuals appears to depend largely on the degree of metabolic dysregulation and metabolic risk factors (glucose intolerance, dyslipidemia, etc.). Notably, interventions that improve insulin sensitivity and cardiorespiratory fitness can reduce CV risk in obese individuals, even in the absence of weight loss.
The cyclic guanylate monophosphate pathway (cGMP) is involved in energy homeostasis and systemic metabolism. Multiple lines of evidence suggest that increasing cGMP activity is beneficial from a metabolic standpoint. Tadalafil is a clinically-available drug that inhibits the enzyme that breaks down cGMP.
The study investigators hypothesize that chronic PDE5 inhibition in obese, insulin-resistant adults will improve cardiometabolic health.
Aim 1: To examine the effect of PDE5 inhibition on energy expenditure. Aim 2: To examine the effect of PDE5 inhibition on insulin sensitivity and secretion.
Aim 3: To examine the effect of PDE5 inhibition on cGMP tone and circulating mediators of cardiometabolic risk.
Tipo di studio
Iscrizione (Effettivo)
Fase
- Fase 2
Contatti e Sedi
Luoghi di studio
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Tennessee
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Nashville, Tennessee, Stati Uniti, 37215
- Vanderbilt University Medical Center
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Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
Inclusion Criteria:
- Adults (ages 21-50)
- Obesity (BMI ≥ 30 kg/m2)
- Prediabetes on oral glucose tolerance test.
Exclusion Criteria:
- Age <21 or > 50
- BMI < 30 kg/m2
- Systolic blood pressure (SBP) < 100, > 150 mmHg
- Current anti-hypertensive medication use, including diuretics
- Current use of organic nitrates
- Current use of PDE-5 inhibitors (sildenafil, tadalafil, vardenafil)
- History of reaction to PDE-5 inhibitors
- Known HIV infection
- Use of medications that strongly alter CYP3A4 activity
- History of myocardial infarction, angina, uncontrolled cardiac arrhythmia, stroke, transient ischemic attack, or seizure
- Known non-arteritic ischemic optic retinopathy (NAIOR)
- History of hearing loss
- Estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 by the modified diet in renal disease (MDRD) equation
- Hepatic transaminase (AST and ALT) levels greater than three times the upper limit of normal
- Known pregnancy or breastfeeding or those unwilling to avoid pregnancy during the course of the study
- History of priapism
- Use in excess of four alcoholic drinks daily
- History of diabetes mellitus or use of anti-diabetic medications
- Known anemia (men, Hct < 38% and women, Hct <36%)
- Menopause
- Inability to exercise on a bicycle
- Weight > 300 pounds
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
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Comparatore attivo: Tadalafil
Subjects will be randomized to one of two arms.
100 obese adult subjects will be randomized to the Tadalafil arm following the screening visit.
Beginning at their baseline visit, they will receive an oral daily dose of Tadalafil (20mg) that they will take for 12 weeks (through their completion of the study).
After randomization has occurred, the active comparator subjects will undergo the following visit protocol: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days).
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Tadalafil is an FDA approved, clinically-available drug that inhibits the enzyme phosphodiesterase type 5A (PDE5).
Subjects who are randomized to this arm will be provided with 20mg of Tadalafil to take every day for 12 weeks, beginning at their baseline visit.
Altri nomi:
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Comparatore placebo: Placebo
Subjects will be randomized to one of two arms.
100 obese adult subjects will be randomized to the placebo arm following the screening visit.
Beginning at their baseline visit, they will receive an oral daily dose of a placebo pill (20mg) that they will take for 12 weeks (through their completion of the study).
After randomization has occurred, the placebo comparator subjects will undergo the following visit protocol: baseline visit (two half-days), an interim visit (6 weeks post-baseline), and a 12-week visit (two half-days).
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100 patients will be randomized to receive a placebo pill.
Subjects in this arm will be provided with 20mg Placebo to take every day for 12 weeks, beginning at their baseline visit.
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
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Resting Energy Expenditure After 12 Weeks of Drug Therapy (kcal/Day)
Lasso di tempo: 12 weeks
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Subjects will undergo a metabolic chamber protocol to measure resting exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement.
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12 weeks
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Insulin Sensitivity After 12 Weeks of Drug Therapy
Lasso di tempo: 12 weeks
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Subjects will undergo an insulin modified fasting intravenous glucose tolerance test (FS-IVGTT) protocol at 12 weeks adjusted statistically for the baseline measurement.
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12 weeks
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Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Physical Activity-induced Energy Expenditure (kcal/Day)
Lasso di tempo: 12 weeks
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During the metabolic chamber protocol, conducted at baseline and at 12 weeks, the cardiopulmonary exercise test protocol will be conducted.
The Energy Expenditure (EE) related to physical activity will be calculated as peak EE above the resting level while performing the exercise test.
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12 weeks
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Dual Energy X-Ray Absorptiometry (DEXA) (g)
Lasso di tempo: 12 weeks
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fat mass at 12 weeks.
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12 weeks
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Quality of Life Using the Medical Outcomes Study Short-Form Health Survey (SF-36) Physical Component Score
Lasso di tempo: 12 weeks
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Quality of life will be assessed using the Medical Outcomes Study Short-Form Health Survey (SF-36).
The SF-36 is a 36 question survey with a total score range from 0-100; higher scores indicate better quality of life.
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12 weeks
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Change in cGMP/NP Ratio After 12 Weeks of Drug Therapy
Lasso di tempo: 12 weeks
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Subjects will undergo a fasting blood draw at baseline and 12 weeks to measure the change in ratio of plasma cyclic guanylate monophosphate pathway (cGMP) to plasma natriuretic peptides (NP) in response to the drug intervention (placebo or tadalafil).
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12 weeks
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Maximal Oxygen Consumption
Lasso di tempo: 12 weeks
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Subjects will undergo a symptom-limited cardiopulmonary exercise test to measure peak oxygen consumption (VO2 max).
Maximal oxygen consumption will be measured as 'mL/min'.
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12 weeks
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Sexual Function
Lasso di tempo: 12 weeks
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The Female Sexual Function Index will be used to measure sexual function in women with a range from 2-36 with higher scores indicating better sexual function.
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12 weeks
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Maximal Exercise Energy Expenditure (kcal/Day)
Lasso di tempo: 12 weeks
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Subjects will undergo a metabolic chamber protocol to measure maximal exercise energy expenditure (kcal/min) at 12 weeks adjusted statistically for the baseline measurement.
Maximal Exercise Energy Expenditure will be measured as "kcal/day"
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12 weeks
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Collaboratori e investigatori
Investigatori
- Investigatore principale: Thomas J Wang, MD, Vanderbilt Cardiovascular Medicine
- Investigatore principale: Evan L Brittain, MD, MSCI, Vanderbilt Cardiovascular Medicine
Studiare le date dei record
Studia le date principali
Inizio studio
Completamento primario (Effettivo)
Completamento dello studio (Effettivo)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Stima)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- 160208
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Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .
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