Systemic Lupus ErythematosusPhase 1/2NCT02338999
Role of PPAR-y Agonists in Immunomodulation and Vascular Prevention in SLE (PPAR-SLE)
A Phase 1/2 study testing PET/CT and Pioglitazone in people with Systemic Lupus Erythematosus, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
Trial summary
Background: Lupus causes a person s immune system to attack the body. It can cause blood vessel problems, heart attack, or stroke. Researchers want to see if the drug pioglitazone may help. Objectives: To see how well pioglitazone improves blood vessel function and decreases blood vessel inflammation. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Systemic Lupus Erythematosus
- What is being tested?
- PET/CT and Pioglitazone
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Jun 2015to 14 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Pregnant or lactating women
- Expected need for major surgery during trial.
- Current or previous diagnosis of malignant disease, except for basal cell or squamous cell carcinoma of the skin with complete excision and clear borders or adequately treated in situ carcinoma of the cervix.
- Acute infections identified during screening that require antibiotics. These subjects would be eligible to participate following resolution of infection before Day 1 visit within the allowed 46 days screening period. The subject will re-screen if it extends beyond the
- allowed 46 days screening period.
- Chronic infections such as hepatitis B, hepatitis C, HIV or Tuberculosis.
Show all 23Show fewer
- Current use of cyclophosphamide or having received cyclophosphamide within the last year.
- Prior history of hemorrhagic cystitis or hematuria while receiving cyclophosphamide that could not be explained by other causes.
- Current use (within 3 months) of tocilizumab, rituximab, belimumab, intravenous gammaglobulin or other biologic.
- History of poor compliance with medical care, study visits and/or medication use.
- Receipt of any investigational new drug or device within 30 days prior to screening or 5 half-lives of the agent <TAB>(whichever is longer), or any investigational new drug with known long-term effects.
- Pioglitazone is not recommended in patients with symptomatic heart failure. Patients with current heart failure (NYHA class II, III or IV) and/or a left ventricular ejection fraction of <45% by echocardiogram at screening will be excluded.
- Significant impairment of major organ function (lung, heart, liver, kidney) or any condition that, in the opinion of the Investigator, would jeopardize the subject s safety following exposure to the study drug.
- Known hypersensitivity to TZDs
- Serum hepatic transaminase levels > 2 times upper normal limit, or clinical evidence of active liver disease at screening. The only exception is patients with confirmed non-alcoholic fatty liver disease (NAFLD) where pioglitazone has been reported to have a therapeutic role.
- Diagnosis of DM or meeting DM criteria at screening visit, as established by new classification criteria: Patients with diabetes are excluded because diabetes by itself will induce profound changes in endothelial function and we want to assess the effects of PPAR agonists in vascular risk beyond changes in insulin resistance.
- Known latex allergy for EndoPAT test
- Patients with severe Raynaud's phenomenon, history of finger ulcers or finger gangrene will not undergo Endopat testing.
- Patients with severe SLE at baseline, as quantified as SLEDAI-2K >20.
- Patients with active lupus nephritis or active CNS lupus at baseline even if SLEDAI-2K <20. Active disease will be considered as CNS or renal disease that require aggressive immunosuppression. Active CNS disease will be diagnosed based on clinical presentation and physical exam, exclusion of other conditions that could explain symptomatology and, when warranted, ancillary tests (imaging) that support the diagnosis.
- Patients that are not on induction therapy for lupus nephritis and have chronic (more than 6 months), stable proteinuria <750 mg/gram in protein:creatinine ratio but otherwise considered to have no evidence of active lupus nephritis (e.g. no cellular casts and stable serum creatinine < 2 mg/dL) over the last 6 months, will be included in the study.
- In selected patients with potentially confounding clinical factors, consults will be requested to help clarify the nature of any underlying renal disease that may affect inclusion.
- Postmenopausal women who have not undergone a DEXA scan over the last year will undergo a DEXA scan at screening. Patients with a better than -2.5 will be included. Postmenopausal women who have undergone a DEXA scan during the last year and have a T score better than -2.5 will be included without repeating the DEXA scan prior to enrollment. If the T score is worse than -2.5, they will be excluded from participating unless the subject is willing to begin appropriate treatment for osteoporosis by Visit Day 1. Postmenopausal women who have undergone a DEXA scan during the last year, have a T score worse than -2.5 and are not on bisphosphonates or other appropriate therapy will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: The Role of PPAR-Gamma Agonists in Immunomodulation and Vascular Prevention in SLE (PPAR-SLE)
Background:
- Lupus causes a person s immune system to attack the body. It can cause blood vessel problems, heart attack, or stroke. Researchers want to see if the drug pioglitazone may help.
Read more
Objectives:
- To see how well pioglitazone improves blood vessel function and decreases blood vessel inflammation. To study its effect on lupus symptoms.
Eligibility:
- Adults at least 18 years old with lupus.
Design:
- Participants will be screened with medical history, heart test, and blood and urine tests. They may have a bone density test.
- Visit 1:
- Participants will have:
- Physical exam and blood drawn.
- Peripheral Arterial Tonometry (Endopat). A cup will be placed on the finger and a pressure cuff on the arm.
- Cardio-ankle vascular index (CAVI) and/or Sphygmocor. Electrodes will be placed on both wrists, a microphone on the chest, and a blood pressure cuff on each arm and leg. Another test will involve placing a small device on a fingertip.
- 18-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) (some participants). A radioactive sugar will be injected into a small plastic tube in an arm vein. Participants will lie on a bed that moves in and out of a scanner that takes pictures.
- Participants will get a 3-month-supply of the study drug or placebo. After 1 week, their dose may increase.
- After those 3 months, they will not take either drug for 8 weeks. Then they will switch and take the other drug for 3 months.
- Participants will have 6 more visits over 8 months after Visit 1. Tests from Visit 1 may be repeated. They may have a urine test.
Read the detailed description
Systemic lupus erythematosus (SLE) is an autoimmune disease of unclear cause that affects primarily women of childbearing age. Patients with lupus have a significantly increased risk of developing complications of their blood vessels due to accelerated hardening of the arteries (atherosclerosis). These complications include heart attacks and stroke. No drug to date has proven to prevent this type of complication in lupus and premature vascular disease significantly impacts the quality of life of these patients and enhances their risk of death.
The thiazolidinediones (TZD) are a class of drugs approved for the treatment of patients with type 2 diabetes mellitus (DM); they belong to the family of drugs that activate the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). They have been proposed to have strong anti-atherogenic and anti-inflammatory effects even in patients without diabetes. Recent work from our group and others indicates that TZDs significantly improve vascular damage, dysfunction of blood vessels and disease activity in mouse models of lupus and abrogate atherosclerosis. We recently identified the TZD pioglitazone as an effective drug in modulation of vascular function and disease activity in patients with rheumatoid arthritis. In addition, we have found in mouse models of lupus and in in vitro experiments with human lupus cells, that pioglitazone has important roles in modulating immune function and vascular manifestations. Furthermore, this drug is not immunosuppressive, adding an additional advantage when compared to other medications used in this disease.
We propose that TZDs could significantly improve blood vessel function and play a role in atherosclerosis prevention in human SLE, in addition to modifying lupus disease activity. The major goal of the proposed research is to assess the effects of the PPAR-gamma agonist pioglitazone in SLE on vascular function and inflammation and on SLE disease activity. The results of the study may lead to the characterization of a new therapeutic target with dual effects on lupus and its associated blood vessel damage
- Conditions
- Systemic Lupus Erythematosus
- Being tested
- PET/CT, Pioglitazone, Placebo
- Keywords
- Autoimmunity Pathogenesis, Atherosclerosis, Adult
- Medical subject headings
- Lupus Erythematosus, Systemic, Atherosclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET/CTRadiation
The combined PET/CT scans provide images that pinpoint the anatomic location of abnormal metabolic activity within the body.
PioglitazoneDrug
Increases insulin sensitivity in muscle and adipose tissue, and inhibits hepatic gluconeogenesis.
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| Pioglitazone, then placebo | Experimental | Treatment with pioglitazone up to 45 mg orally daily for three months. Followed by a two-month washout period before cross over to placebo orally daily for three months. A randomly selected subset of subjects underwent optional FDG-PET/CT for measurement of inflammatory activity in the blood vessels. Receives: Radiation: PET/CT; Drug: Pioglitazone; Drug: Placebo |
| Placebo, then Pioglitazone | Experimental | Treatment with placebo orally daily for three months. Followed by a two-month washout period before cross over to pioglitazone up to 45 mg daily orally for an additional three months. A randomly selected subset of subjects underwent optional FDG-PET/CT for measurement of inflammatory activity in the blood vessels. Receives: Radiation: PET/CT; Drug: Pioglitazone; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Vascular Function and Cardiometabolic Risk as Measured by Left CAVI at Month 3
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI).
CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Measured: 3 months after start of first intervention (Baseline to 3 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by Left CAVI at Month 8
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI).
CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Measured: 3 months after start of second intervention (5 months to 8 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by Right CAVI at Month 3
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI).
CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Measured: 3 months after start of first intervention (Baseline to 3 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by Right CAVI at Month 8
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI).
CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Measured: 3 months after start of second intervention (5 months to 8 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by PWV at Month 3
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Pulse, wave, velocity (PWV).
The central aortic pressure PWV was determined by using the pressure tonometer and an EKG signal was used simultaneously to visualize ventricular-vascular interactions. It increases with atherosclerosis progression. Central aortic BP and stiffness were quantified using SphygmoCor CP system (AtCor Medical Pty Ltd.; New South Wales, Australia).
Measured: 3 months after start of first intervention (Baseline to 3 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by PWV at Month 8
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Pulse, wave, velocity (PWV).
The central aortic pressure PWV was determined by using the pressure tonometer and an EKG signal was used simultaneously to visualize ventricular-vascular interactions. It increases with atherosclerosis progression. Central aortic BP and stiffness were quantified using SphygmoCor CP system (AtCor Medical Pty Ltd.; New South Wales, Australia).
Measured: 3 months after start of second intervention (5 months to 8 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by RHI at Month 3
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Reactive hyperemia index (RHI).
RHI is a measure of endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT). It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. The possible range of scores is 1 to 3. Increasing score indicates the improvement of coronary endothelial function
Measured: 3 months after start of first intervention (Baseline to 3 months)
Change in Vascular Function and Cardiometabolic Risk as Measured by RHI at Month 8
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Reactive hyperemia index (RHI).
RHI is a measure of endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT). It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. The possible range of scores is 1 to 3. Increasing score indicates the improvement of coronary endothelial function
Measured: 3 months after start of second intervention (5 months to 8 months)
Effect of Pioglitazone on Vascular Inflammation and Cardiometabolic Risk as Measured by TBR Value at Month 3
Change in vascular inflammation using non-invasive vascular test, measuring changes in target to blood pool ratio (TBR) value by positron emission tomography (PET) computerized tomography (CT). The higher the value, the higher the degree of vascular inflammation.
Measured: 3 months after start of first intervention (Baseline to 3 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2015 (estimated)
- Study start18 Jun 2015
- Primary completion14 Jul 2020
- Study completion14 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
- 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
- Phase 1/2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mariana J Kaplan, M.D., Principal investigator, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02338999
- Sponsor's protocol ID
- 150060
- Other IDs
- 15-AR-0060
- Status last verified
- 14 Jul 2020
- First submitted
- 14 Jan 2015
- Last updated
- 14 Sep 2021
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Hasni S, Temesgen-Oyelakin Y, Davis M, Chu J, Poncio E, Naqi M, Gupta S, Wang X, Oliveira C, Claybaugh D, Dey A, Lu S, Carlucci P, Purmalek M, Manna ZG, Shi Y, Ochoa-Navas I, Chen J, Mukherjee A, Han KL, Cheung F, Koroleva G, Belkaid Y, Tsang JS, Apps R, Thomas DE, Heller T, Gadina M, Playford MP, Li X, Mehta NN, Kaplan MJ. Peroxisome proliferator activated receptor-gamma agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus. Ann Rheum Dis. 2022 Oct 12;81(11):1576-1584. doi: 10.1136/ard-2022-222658.
PubMed 35914929
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of PPAR-Gamma Agonists in Immunomodulation and Vascular Prevention in SLE (PPAR-SLE)
- ClinicalTrials.gov ID
- NCT02338999
- Acronym / sponsor ID
- 150060
- Conditions
- Systemic Lupus Erythematosus
- Keywords
- Autoimmunity Pathogenesis, Atherosclerosis, Adult
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)US National Institutes of Health
- Study start
- 18 Jun 2015 (actual)
- Primary completion
- 14 Jul 2020 (actual)
- Study completion
- 14 Jul 2020 (actual)
- First posted
- 15 Jan 2015 (estimated)
- Results
- Posted 14 Sep 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Lupus causes a person s immune system to attack the body. It can cause blood vessel problems, heart attack, or stroke. Researchers want to see if the drug pioglitazone may help.
Objectives:
- To see how well pioglitazone improves blood vessel function and decreases blood vessel inflammation. To study its effect on lupus symptoms.
Eligibility:
- Adults at least 18 years old with lupus.
Design:
- Participants will be screened with medical history, heart test, and blood and urine tests. They may have a bone density test.
- Visit 1:
- Participants will have:
- Physical exam and blood drawn.
- Peripheral Arterial Tonometry (Endopat). A cup will be placed on the finger and a pressure cuff on the arm.
- Cardio-ankle vascular index (CAVI) and/or Sphygmocor. Electrodes will be placed on both wrists, a microphone on the chest, and a blood pressure cuff on each arm and leg. Another test will involve placing a small device on a fingertip.
- 18-Fluorodeoxyglucose (FDG) positron emission tomography/computerized tomography (PET/CT) (some participants). A radioactive sugar will be injected into a small plastic tube in an arm vein. Participants will lie on a bed that moves in and out of a scanner that takes pictures.
- Participants will get a 3-month-supply of the study drug or placebo. After 1 week, their dose may increase.
- After those 3 months, they will not take either drug for 8 weeks. Then they will switch and take the other drug for 3 months.
- Participants will have 6 more visits over 8 months after Visit 1. Tests from Visit 1 may be repeated. They may have a urine test.
Detailed description
Systemic lupus erythematosus (SLE) is an autoimmune disease of unclear cause that affects primarily women of childbearing age. Patients with lupus have a significantly increased risk of developing complications of their blood vessels due to accelerated hardening of the arteries (atherosclerosis). These complications include heart attacks and stroke. No drug to date has proven to prevent this type of complication in lupus and premature vascular disease significantly impacts the quality of life of these patients and enhances their risk of death.
The thiazolidinediones (TZD) are a class of drugs approved for the treatment of patients with type 2 diabetes mellitus (DM); they belong to the family of drugs that activate the peroxisome proliferator-activated receptor-gamma (PPAR-gamma). They have been proposed to have strong anti-atherogenic and anti-inflammatory effects even in patients without diabetes. Recent work from our group and others indicates that TZDs significantly improve vascular damage, dysfunction of blood vessels and disease activity in mouse models of lupus and abrogate atherosclerosis. We recently identified the TZD pioglitazone as an effective drug in modulation of vascular function and disease activity in patients with rheumatoid arthritis. In addition, we have found in mouse models of lupus and in in vitro experiments with human lupus cells, that pioglitazone has important roles in modulating immune function and vascular manifestations. Furthermore, this drug is not immunosuppressive, adding an additional advantage when compared to other medications used in this disease.
We propose that TZDs could significantly improve blood vessel function and play a role in atherosclerosis prevention in human SLE, in addition to modifying lupus disease activity. The major goal of the proposed research is to assess the effects of the PPAR-gamma agonist pioglitazone in SLE on vascular function and inflammation and on SLE disease activity. The results of the study may lead to the characterization of a new therapeutic target with dual effects on lupus and its associated blood vessel damage
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Pioglitazone, then placebo | Experimental | Radiation: PET/CT, Drug: Pioglitazone, Drug: PlaceboTreatment with pioglitazone up to 45 mg orally daily for three months. Followed by a two-month washout period before cross over to placebo orally daily for three months. A randomly selected subset of subjects underwent optional FDG-PET/CT for measurement of inflammatory activity in the blood vessels. |
| Placebo, then Pioglitazone | Experimental | Radiation: PET/CT, Drug: Pioglitazone, Drug: PlaceboTreatment with placebo orally daily for three months. Followed by a two-month washout period before cross over to pioglitazone up to 45 mg daily orally for an additional three months. A randomly selected subset of subjects underwent optional FDG-PET/CT for measurement of inflammatory activity in the blood vessels. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (23 listed)
- Pregnant or lactating women
- Expected need for major surgery during trial.
- Current or previous diagnosis of malignant disease, except for basal cell or squamous cell carcinoma of the skin with complete excision and clear borders or adequately treated in situ carcinoma of the cervix.
- Acute infections identified during screening that require antibiotics. These subjects would be eligible to participate following resolution of infection before Day 1 visit within the allowed 46 days screening period. The subject will re-screen if it extends beyond the
- allowed 46 days screening period.
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 |
|---|---|---|
| PET/CTThe combined PET/CT scans provide images that pinpoint the anatomic location of abnormal metabolic activity within the body. | Radiation | Pioglitazone, then placebo, Placebo, then Pioglitazone |
| PioglitazoneIncreases insulin sensitivity in muscle and adipose tissue, and inhibits hepatic gluconeogenesis. | Drug | Pioglitazone, then placebo, Placebo, then Pioglitazone |
| Placebo | Drug | Pioglitazone, then placebo, Placebo, then Pioglitazone |
Primary outcome
Change in Vascular Function and Cardiometabolic Risk as Measured by Left CAVI at Month 3
Time frame: 3 months after start of first intervention (Baseline to 3 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI). CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Change in Vascular Function and Cardiometabolic Risk as Measured by Left CAVI at Month 8
Time frame: 3 months after start of second intervention (5 months to 8 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI). CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Change in Vascular Function and Cardiometabolic Risk as Measured by Right CAVI at Month 3
Time frame: 3 months after start of first intervention (Baseline to 3 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI). CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Change in Vascular Function and Cardiometabolic Risk as Measured by Right CAVI at Month 8
Time frame: 3 months after start of second intervention (5 months to 8 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance - Cardio ankle vascular index (CAVI). CAVI is an index reflecting the stiffness of the artery from the heart to ankles; it increases with atherosclerosis progression. CAVI was measured using VaSera-1500A (Fukuda Denshi Co. Redmond, WA)
Change in Vascular Function and Cardiometabolic Risk as Measured by PWV at Month 3
Time frame: 3 months after start of first intervention (Baseline to 3 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Pulse, wave, velocity (PWV). The central aortic pressure PWV was determined by using the pressure tonometer and an EKG signal was used simultaneously to visualize ventricular-vascular interactions. It increases with atherosclerosis progression. Central aortic BP and stiffness were quantified using SphygmoCor CP system (AtCor Medical Pty Ltd.; New South Wales, Australia).
Change in Vascular Function and Cardiometabolic Risk as Measured by PWV at Month 8
Time frame: 3 months after start of second intervention (5 months to 8 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Pulse, wave, velocity (PWV). The central aortic pressure PWV was determined by using the pressure tonometer and an EKG signal was used simultaneously to visualize ventricular-vascular interactions. It increases with atherosclerosis progression. Central aortic BP and stiffness were quantified using SphygmoCor CP system (AtCor Medical Pty Ltd.; New South Wales, Australia).
Change in Vascular Function and Cardiometabolic Risk as Measured by RHI at Month 3
Time frame: 3 months after start of first intervention (Baseline to 3 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Reactive hyperemia index (RHI). RHI is a measure of endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT). It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. The possible range of scores is 1 to 3. Increasing score indicates the improvement of coronary endothelial function
Change in Vascular Function and Cardiometabolic Risk as Measured by RHI at Month 8
Time frame: 3 months after start of second intervention (5 months to 8 months)
Change in vascular function using non-invasive vascular tests, measuring vascular compliance -Reactive hyperemia index (RHI). RHI is a measure of endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT). It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post-to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered sign of endothelial dysfunction and RHI equal to or greater than 1.67 is considered normal function. The possible range of scores is 1 to 3. Increasing score indicates the improvement of coronary endothelial function
Effect of Pioglitazone on Vascular Inflammation and Cardiometabolic Risk as Measured by TBR Value at Month 3
Time frame: 3 months after start of first intervention (Baseline to 3 months)
Change in vascular inflammation using non-invasive vascular test, measuring changes in target to blood pool ratio (TBR) value by positron emission tomography (PET) computerized tomography (CT). The higher the value, the higher the degree of vascular inflammation.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35914929Hasni S, Temesgen-Oyelakin Y, Davis M, Chu J, Poncio E, Naqi M, Gupta S, Wang X, Oliveira C, Claybaugh D, Dey A, Lu S, Carlucci P, Purmalek M, Manna ZG, Shi Y, Ochoa-Navas I, Chen J, Mukherjee A, Han KL, Cheung F, Koroleva G, Belkaid Y, Tsang JS, Apps R, Thomas DE, Heller T, Gadina M, Playford MP, Li X, Mehta NN, Kaplan MJ. Peroxisome proliferator activated receptor-gamma agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus. Ann Rheum Dis. 2022 Oct 12;81(11):1576-1584. doi: 10.1136/ard-2022-222658.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
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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.
Mariana J Kaplan, M.D. principal investigator
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PET/CT and Pioglitazone in people with Systemic Lupus Erythematosus, run by National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at 1 site in United States.
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 0 inclusion and 23 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: finished, as of the sponsor's last update on 14 Sep 2021. 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 United States. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Sep 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Vascular Function and Cardiometabolic Risk as Measured by Left CAVI at Month 3 (time frame: 3 months after start of first intervention (Baseline to 3 months)). The study lists 9 primary outcomes in all. 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 NCT02338999, 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 14 Sep 2021.