Pulmonary Arterial HypertensionEarly Phase 1NCT02023450
Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
A Early Phase 1 study testing saquinavir and ritonavir in people with Pulmonary Arterial Hypertension, run by The Third Xiangya Hospital of Central South University at 1 site in China.
Trial summary
Study Rationale:There is recent evidence that HIV protease inhibitors (HIV-PI) can improve pulmonary hemodynamics in experimental models of pulmonary arterial hypertension (PAH). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Pulmonary Arterial Hypertension
- What is being tested?
- saquinavir and ritonavir
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteChina
- Study dates
- Dec 2013to Jul 2015
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Age 18-60
- Idiopathic pulmonary arterial hypertension
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study
- Had the diagnosis of PAH confirmed by a cardiac catheterization:Mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg (at rest)，a pulmonary capillary wedge pressure equal or less than 15mmHg, and a normal or reduced cardiac output
- Stable PAH therapy for at least 3 months
Who cannot join
- Baseline systemic hypotension, defined as MAP less than 50 mmHg
- Required intravenous inotropes within 30 days prior to study participation
- Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at screening
- Has a history of portal hypertension or chronic liver disease, including cirrhosis, chronic alcoholism, hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as moderate to severe hepatic impairment (Child-Pugh Class B-C)
- Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at screening or requires dialysis support
- Has a hemoglobin concentration <9 g/dL at Screening
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- History of atrial septostomy
- Repaired or unrepaired congenital heart disease (CHD)
- Pericardial constriction
- Restrictive or congestive cardiomyopathy
- Left ventricular ejection fraction 40% by multiple gated acquisition scan (MUGA), angiography or echocardiography
- Symptomatic coronary disease with demonstrable ischemia
- Other severe acute or chronic medical or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
- Has a psychiatric, addictive or other disorder that compromises the ability to give informed consent for participating in this study. This includes subjects with a recent history of abusing alcohol or illicit drugs 30 days prior to study screening Day 1 and for the duration of the study
- Poorly controlled asthma defined by active wheezing and/or cough with FEV1 < 70% predicted, responsive to inhaled BD (>15% increase in FEV1 with BD)
- Clinically significant intercurrent illness (including lower respiratory tract infection) or clinically significant surgery within 4 weeks before the administration of study drug
- History of hypersensitivity or idiosyncratic reaction to drugs from multiple drug classes
- Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days (or 5 half lives of the drug, whichever is longer) before the first dose of study drug
- Blood loss or blood donation >550mL within 90 days or plasma donation >500 mL within 14 days before administration of study drug;
- Patients with a QTc interval > 450 msec
- Has diabetes mellitus as defined by symptoms of hyperglycemia and serum fasting plasma glucose level≥7.0mmol/l or casual plasma glucose≥11.1mmol/l at screen
- Has a hyperlipidemia as TC≥6.22 mmol/L, LDL-C ≥4.14 mmol/L or TG ≥2.26 mmol/L
- History of crohn's disease, ulcerative colitis (UC) and etc. Inflammatory bowel disease (IBD)
- Patients who are not willing to take contraceptive measures during the study
- Patients who are taking certain other medication will need to be evaluated for possible exclusion based on the potential for adverse drug interactions
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Xiangya hospital
Changsha, Hunan
YU ZAI XIN, PhD, 0086-13875873205, yuzaixin@126.com
About this study
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.
Read more
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.
- Conditions
- Pulmonary Arterial Hypertension
- Being tested
- saquinavir and ritonavir
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
saquinavir and ritonavirDrug
micro and low dose
saquinavir and ritonavirDrug
standard dose
| Study group | Role | What they receive |
|---|---|---|
| micro/low dose saquinavir and ritonavir | Experimental | To determine if micro dose and low dose SQV+RIT mediates parameters of chronic inflammation in patients with IPAH. Receives: Drug: saquinavir and ritonavir |
| standard dose saquinavir and ritonavir | Experimental | 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. Receives: Drug: saquinavir and ritonavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
HMGB1 level
Measured: 14 days
Secondary outcomes (4)
TNF、IL-1Β、IL-6、NT-ProBNP and CRP level
Measured: 14 days
NYHA/WHO functional class
Measured: 14 days
Brog respiration class
Measured: 14 days
PA pressure and total right heart function measured by echocardiography
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2013 (estimated)
- Study startDec 2013
- Primary completionDec 2014 (estimated)
- Study completionJul 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by The Third Xiangya Hospital of Central South UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Xiangya Hospital of Central South University
- Responsible party
- Principal investigator, Yuan Hong, The Third Xiangya Hospital of Central South University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02023450
- Sponsor's protocol ID
- HPI-PAH-0
- Status last verified
- Sep 2014
- First submitted
- 23 Dec 2013
- Last updated
- 8 Sep 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Li Y, Li XH, Yu ZX, Cai JJ, Billiar TR, Chen AF, Lv B, Chen ZY, Huang ZJ, Yang GP, Song J, Liu B, Yuan H. HIV protease inhibitors in pulmonary hypertension: rationale and design of a pilot trial in idiopathic pulmonary arterial hypertension. Pulm Circ. 2015 Sep;5(3):538-46. doi: 10.1086/682426.
PubMed 26401255
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Testing of HIV Protease Inhibitors to Suppress Inflammation and Improve Cardio Pulmonary Hemodynamics in Subjects With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT02023450
- Acronym / sponsor ID
- HPI-PAH-0
- Conditions
- Pulmonary Arterial Hypertension
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- The Third Xiangya Hospital of Central South UniversityUniversity, hospital or other
- Collaborators
- Xiangya Hospital of Central South University
- Study start
- Dec 2013
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Jul 2015 (estimated)
- First posted
- 30 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| micro/low dose saquinavir and ritonavir | Experimental | Drug: saquinavir and ritonavirTo determine if micro dose and low dose SQV+RIT mediates parameters of chronic inflammation in patients with IPAH. |
| standard dose saquinavir and ritonavir | Experimental | Drug: saquinavir and ritonavirTo 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age 18-60
- Idiopathic pulmonary arterial hypertension
- Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study
- Had the diagnosis of PAH confirmed by a cardiac catheterization:Mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg (at rest)，a pulmonary capillary wedge pressure equal or less than 15mmHg, and a normal or reduced cardiac output
- Stable PAH therapy for at least 3 months
Key exclusion criteria (25 listed)
- Baseline systemic hypotension, defined as MAP less than 50 mmHg
- Required intravenous inotropes within 30 days prior to study participation
- Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure >160 mm Hg or sitting diastolic blood pressure >100 mm Hg at screening
- Has a history of portal hypertension or chronic liver disease, including cirrhosis, chronic alcoholism, hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as moderate to severe hepatic impairment (Child-Pugh Class B-C)
- Has chronic renal insufficiency as defined by serum creatinine >2.5 mg/dL at screening or requires dialysis support
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| saquinavir and ritonavirmicro and low dose | Drug | micro/low dose saquinavir and ritonavir |
| saquinavir and ritonavirstandard dose | Drug | standard dose saquinavir and ritonavir |
Primary outcome
HMGB1 level
Time frame: 14 days
4 secondary outcomes
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2014.
- Derived from this study: PubMed 26401255Li Y, Li XH, Yu ZX, Cai JJ, Billiar TR, Chen AF, Lv B, Chen ZY, Huang ZJ, Yang GP, Song J, Liu B, Yuan H. HIV protease inhibitors in pulmonary hypertension: rationale and design of a pilot trial in idiopathic pulmonary arterial hypertension. Pulm Circ. 2015 Sep;5(3):538-46. doi: 10.1086/682426.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing saquinavir and ritonavir in people with Pulmonary Arterial Hypertension, run by The Third Xiangya Hospital of Central South University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Li Ying, MD (0086-13787184360, lydia0312@csu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
HMGB1 level (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02023450, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2014.