Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
|ClinicalTrials.gov Identifier: NCT02023450|
Recruitment Status : Unknown
Verified September 2014 by Yuan Hong, The Third Xiangya Hospital of Central South University.
Recruitment status was: Recruiting
First Posted : December 30, 2013
Last Update Posted : September 8, 2014
Study Rationale:There is recent evidence that HIV protease inhibitors (HIV-PI) can improve pulmonary hemodynamics in experimental models of pulmonary arterial hypertension (PAH). There is also experimental evidence that both TLR4 and high mobility group box 1 (HMGB1) participate in the pathogenesis of experimental pulmonary hypertension. A recent high throughput screen for inhibitors of HMGB1 induced macrophage activation yielded HIV-protease inhibitors (PIs) as potent inhibitors of HMGB1 induced cytokine production. Based on the experimental evidence we propose a trial to determine whether HIV-PIs will alter the pathobiology of PAH.
Study Objectives:The main objective of this study is to determine whether saquinavir and ritonavir (SQV+RIT) which have a well-characterized safety profile in humans will reduce bio markers of inflammation and pulmonary artery pressures in patients with PAH.
Study Hypothesis:We hypothesize that the HIV-PI, SQV+RIT, will reduce circulating parameters of inflammation including HMGB1, IL1-beta, IL-6, IL-8, IL-10, TNF-alpha and CRP. Our end points will be changes in these parameters from baseline over the duration of the study.We hypothesize that treatment with SQV+RIT will reduce pulmonary artery(PA) pressure of patients with PAH as measured by echocardiography.
Study Design:This is a single center open label phase 0 study to evaluate the effect of SQV +RIT in patients with IPAH. Subjects with IPAH(N=20) will be enrolled into a study, which will be divided into 3 cohorts and entail the administration of HIV protease inhibitors in three doses. The first cohort (n=3) will receive a starting dose of SQV 0.3 mg/kg twice daily in combination with RIT 0.03 mg/kg twice daily. If the first dose is well-tolerated, the second cohort (n= 3 ) with IPAH will be given doses of SQV 3 mg/kg and RIT 0.3 mg/kg twice daily. If the second dose is well-tolerated, the last cohort (n= 14 ) with IPAH will be given doses of SQV 15 mg/kg and RIT 1.5 mg/kg twice daily.
|Condition or disease||Intervention/treatment||Phase|
|Pulmonary Arterial Hypertension||Drug: saquinavir and ritonavir||Early Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Study Start Date :||December 2013|
|Estimated Primary Completion Date :||December 2014|
|Estimated Study Completion Date :||July 2015|
Experimental: micro/low dose saquinavir and ritonavir
To determine if micro dose and low dose SQV+RIT mediates parameters of chronic inflammation in patients with IPAH.
Drug: saquinavir and ritonavir
micro and low dose
Experimental: standard dose saquinavir and ritonavir
To determine if short-term use of SQV+RIT reduces parameters of chronic inflammation and PA pressure of IPAH based on echocardiographic parameters. Safety issue also evaluated at the same time.
Drug: saquinavir and ritonavir
- HMGB1 level [ Time Frame: 14 days ]
- TNF、IL-1Β、IL-6、NT-ProBNP and CRP level [ Time Frame: 14 days ]
- NYHA/WHO functional class [ Time Frame: 14 days ]
- Brog respiration class [ Time Frame: 14 days ]
- PA pressure and total right heart function measured by echocardiography [ Time Frame: 14 days ]
- 6 minute walk distance [ Time Frame: 14 days ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02023450
|Contact: Li Ying, MDemail@example.com|
|Changsha, Hunan, China|
|Contact: YU ZAI XIN, PhD 0086-13875873205 firstname.lastname@example.org|