A Trial to Determine the Effect of Psoriasis Treatment on Cardiometabolic Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 9
- 主要终点
- Change in Vascular Inflammation
研究概览
简要总结
The purpose of this study is to assess the effect of adalimumab (Humira), when compared to NB-UVB (narrow-band ultraviolet B) phototherapy or placebo (an inactive substance that may resemble an active substance but has no medical value) injection. The study will compare the effects of each on systemic inflammation and cardiovascular disease risk factors in subjects diagnosed with moderate to severe psoriasis.
This study will look for systemic vascular inflammation in subjects with a test called FDG-PET/CT (Fluorodeoxyglucose-positron emission tomography/computed tomography). The study will also look for cardio metabolic (heart disease and metabolic factors such as diabetes) identifiers in the blood. A blood sample will be taken that will look for these markers identifying high cholesterol, cholesterol efflux function (the ability of cholesterol to move in the body), metabolic factors, and inflammation.
This study will also assess the effect of adalimumab (Humira), when compared to NB-UVB phototherapy or placebo injection on psoriasis activity and severity. The study will also compare the safety of adalimumab (Humira) to NB-UVB phototherapy or placebo injection. This study will also evaluate subjects' reported outcomes through a questionnaire that will assess quality-of-life in subjects living with psoriasis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males and females 18 years of age and older.
- •Clinical diagnosis of psoriasis for at least 6 months as determined by subject interview of his/her medical history and confirmation of diagnosis through physical examination by Investigator.
- •Stable plaque psoriasis for at least 2 months before Screening and at Baseline (Week 0) as determined by subject interview of his/her medical history.
- •Moderate to severe psoriasis defined by ≥ 10 percent Body Surface Area (BSA) involvement at the Baseline (Week 0) visit.
- •PASI (psoriasis assessment and severity index) score of ≥ 12 at the Baseline (Week 0) visit.
- •Subject is a candidate for systemic therapy or phototherapy and has active psoriasis despite prior treatment with topical agents.
- •Women are eligible to participate in the study if they meet one of the following criteria:
- •Women of childbearing potential who are willing to undergo regular pregnancy testing and agree to use one method of contraception throughout the study are eligible to participate
- •Women who are postmenopausal (for at least one year), sterile, or hysterectomized are eligible to participate
- •Women who have undergone tubal ligation are eligible to participate
- •Women who agree to be sexually abstinent, defined as total abstinence from sexual intercourse, as a form of contraception are eligible to participate in the study.
- •Subject is judged to be in good general health as determined by the Principal Investigator based upon the results of medical history, laboratory profile, physical examination, and 12-lead electrocardiogram (ECG) performed at screening.
- •Able and willing to give written informed consent and to comply with requirements of this study protocol.
排除标准
- •Previous adverse event following exposure to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies and contraindicates future treatment.
- •Previous lack of response to a TNF-alpha antagonist and/or UV phototherapy that led to discontinuation of either of these therapies.
- •Diagnosis of erythrodermic psoriasis, generalized or localized pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis.
- •Diagnosis of other active skin diseases or skin infections (bacterial, fungal, or viral) that may interfere with evaluation of psoriasis.
- •Cannot avoid UVB phototherapy for at least 14 days prior to the Baseline (Week 0) visit.
- •Cannot avoid psoralen-UVA phototherapy for at least 30 days prior to the Baseline (Week 0) visit and during the study.
- •Cannot discontinue systemic therapies for the treatment of psoriasis, or systemic therapies known to improve psoriasis, during the study:
- •Systemic (investigational or marketed) therapies must be discontinued at least 30 days prior to the Baseline (Week 0) visit except for biologics.
- •All biologics, except ustekinumab, must be discontinued for at least 90 days prior to Baseline (Week 0).
- •The IL-12/IL-23 antagonist ustekinumab (half-life of 45.6 ± 80.2 days) must be discontinued for at least 180 days prior to Baseline (Week 0).
- •Investigational agents must be discontinued at least 30 days or 5 half-lives (whichever is longer) prior to the Baseline (Week 0) visit.
- •Subject is taking or requires oral or injectable corticosteroids during the study. Inhaled corticosteroids for stable medical conditions are allowed.
- •Poorly controlled medical condition, such as unstable ischemic heart disease, congestive heart failure, recent cerebrovascular accidents, psychiatric disease requiring frequent hospitalization, and any other condition, which, in the opinion of the Investigator, would put the subject at risk by participation in the study.
- •History of diabetes mellitus, type 1 or type 2 - note that patients with type 2 diabetes may be enrolled if the duration of diabetes is <10 years and HbA1c is <7.0%)
- •Uncontrolled hypertension, with measured systolic blood pressure >180 mmHg or diastolic blood pressure >90 mmHg
- •History of demyelinating diseases or lupus.
- •Subject has infection or risk factors for severe infections, for example:
- •Positive serology or known history of HIV, hepatitis B or C, or other severe, recurrent, or persistent infections;
- •Excessive immunosuppression or other factors associated with it, including human immunodeficiency virus infection;
- •Active tuberculosis (TB) disease;
- •Evidence of latent TB infection demonstrated by Purified Protein Derivative (PPD) ≥ 5 mm of induration or positive Quantiferon-GOLD results; except if prophylactic treatment for TB, as recommended by local guidelines, is initiated prior to administration of study drug or if there is documentation that the subject has received prophylactic treatment for TB previously.
- •Any other significant infection requiring hospitalization or intravenous (IV) antibiotics in the month prior to Baseline;
- •Infection requiring treatment with oral or parenteral antibiotics within 14 days prior to Baseline;
- •Subject has received vaccination with Bacille Calmette-Guerin (BCG) within 365 days prior to Screening;
- •Subject has received vaccination with a live viral agent 30 days prior to Screening or will require a live vaccination during study participation including up to 30 days after the last dose of study drug.
- •Subject has history of hematological or solid malignancy other than successfully treated basal cell carcinoma, non-metastatic cutaneous squamous cell carcinoma or cervical carcinoma in situ.
- •Female subject who is pregnant or breast-feeding or considering becoming pregnant during the study.
- •Screening clinical laboratory analyses showing any of the following abnormal results:
- •Hemoglobin (Hgb) < 10 g/dL in females or <12 g/dL in males;
- •White blood cell (WBC) count <2.5 x 109/L
- •o Subject can be included if WBC count is <2.5 x x 109/L and absolute neutrophil count (ANC) is >1000 cells / mm
- •WBC count > 15 x 109/L;
- •Platelet count < 100 x 109/L;
- •Serum aspartate transaminase (AST) or alanine transaminase (ALT) >2.5 upper limits of normal (ULN);
- •Serum total bilirubin ≥2 mg/dL (≥26 µmol/L); or
- •Serum creatinine >1.6 mg/dL (>141 µmol/L).
- •Recent history of substance abuse or psychiatric illness that could preclude compliance with the protocol.
- •History of any substance abuse within 365 days of screening visit
- •Alcohol use >14 drinks per week at the screening visit or within 30 days of the screening period
- •If subject is on cholesterol-lowering medication (e.g. statin), dose and form of medication must be stable for 90 days prior to week 0 and remain stable throughout the duration of the study.
- •History of photosensitivity of medical condition that may be exacerbated by UV exposures such as lupus or dermatomyositis
研究组 & 干预措施
Adalimumab (Humira)
Injection of the active drug Humira.
干预措施: Adalimumab (Humira) (Drug)
Placebo Injection
Injection of placebo in place of active Humira injection.
干预措施: Placebo Injection (Drug)
NB-UVB phototherapy
NB-UVB Phototherapy 3 times per week, no other intervention.
干预措施: NB-UVB phototherapy (Other)
结局指标
主要结局
Change in Vascular Inflammation
时间窗: Baseline - Week 12
Change in total vascular inflammation of five aortic segments as assessed on FDG-PET/CT between baseline and week 12. The arterial uptake of FDG is measured by the standardized uptake value (SUV) max divided by the venous SUV mean yielding a target to background ratio (TBR).
Change in Cardiometabolic Biomarkers: High Density Lipoprotein Particle Total
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on high density lipoprotein particle total.
Change in Cardiometabolic Biomarkers: Log Interleukin 6
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log interleukin 6.
Change in Cardiometabolic Biomarkers: Cholesterol Efflux
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on cholesterol efflux capacity. The ability to promote cholesterol efflux from macrophages is a classic function of HDL that is thought to be an important mechanism by which HDL protects against atherosclerosis. HDL cholesterol efflux capacity assays are performed based on published methods using J774 cells derived from a murine macrophage cell line (Mehta NN Atherosclerosis 2012). Efflux is calculated as a unitless measure by using the following formula: \[(µCi of 3H-cholesterol in media containing apoB-depleted subject plasma - µCi of 3H-cholesterol in plasma-free media) / (µCi of 3H-cholesterol in media containing apoB-depleted pooled control plasma-µCi of 3H-cholesterol in pooled control plasma-free media)\]. The pooled plasma was obtained from five healthy volunteers.
Change in Cardiometabolic Biomarkers: Total Cholesterol
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on total cholesterol.
Change in Cardiometabolic Biomarkers: Log C-reactive Protein
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log C-reactive protein (CRP).
Change in Cardiometabolic Biomarkers: GlycA
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on GlycA
Change in Cardiometabolic Biomarkers: Log Insulin
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log insulin.
Change in Cardiometabolic Biomarkers: Log Adiponectin
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log adiponectin.
Change in Cardiometabolic Biomarkers: Low Density Lipoprotein Particle Total
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on low density lipoprotein particle total.
Change in Cardiometabolic Biomarkers: Log Leptin
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log leptin.
Change in Cardiometabolic Biomarkers: Log Tumor Necrosis Factor-alpha
时间窗: Baseline - Week 12
To assess the effects of adalimumab, as compared to NB-UVB phototherapy or placebo, in patients with moderate to severe psoriasis on log Tumor necrosis factor-alpha.
次要结局
- Change in Psoriasis Activity (PASI-75 and PGA)(Baseline - Week 12)
- Change in Patient-reported Outcomes-Dermatology Life Quality Index (DLQI)(Baseline - Week 12)
- Change in Patient-reported Outcomes-MEDFICTS Dietary Assessment)(Baseline to Week 12)
- Number of Patients With Adverse Events.(Baseline - Week 12)
- Change in Patient-reported Outcomes-EuroQol EQ-5D(Baseline -Week 12)
- Change in Patient-reported Outcomes-International Physical Activity Questionnaire (IPAQ)(Baseline week 4, 8 and 12)