Clinical Study on Circadian Genes Dysregulation in Patients With Glucocorticoid Disorders
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 44
- 试验地点
- 2
- 主要终点
- Circadian genes CLOCK and ARNTL expression evaluation
研究概览
简要总结
This is a multicentric, prospective, intervention study on circadian genes expression in peripheral blood mononuclear cells as biomarkers of circadian rhythm derangement in patients affected by alterations of endogenous glucocorticoids secretion (Cushing's Syndrome during active phase, treatment and under remission and newly or on established glucocorticoid replacement therapy adrenal insufficiency)
详细描述
This is an intervention, prospective, multicentric study.
Enrolled patients will undergo 4 visits:
- Adrenal insufficiency (AI) patients: patients affected by primary or secondary adrenal insufficiency, whether newly diagnosed or on established glucocorticoid therapy, will be evaluated at baseline and after one, three and six months.
- Cushing's Syndrome (CS) patients: patients affected by Cushing's Syndrome will be evaluated at baseline during active phase of the disease and one, three and six months after treatment or remission. Patients affected by Cushing's Syndrome who will require glucocorticoid replacement therapy after remission will be evaluated three and six months after remission and then three and six months after the eventual glucocorticoid replacement therapy withdrawal. CS treatment will be surgery or medical therapy according to guidelines. Timing of medical therapy administration will change during protocol according to circadian rhythms.
Age-, sex- and BMI- matched healthy controls will be enrolled. Patients and controls will undergo the same procedures at baseline and after 1, 3 and 6 months.
The primary outcome measure will be the evaluation of circadian genes CLOCK and Aryl Hydrocarbon Receptor Nuclear Translocator Like (ARNTL) expression in peripheral blood mononuclear cells (PBMC) compared to healthy controls.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Primary or secondary chronic adrenal insufficiency, previously or newly diagnosed.
- •ACTH-dependent or ACTH-independent Cushing's Syndrome diagnosis during active disease (new diagnosis or recidivating).
- •Signed informed consent to participate in the study.
排除标准
- •- acute adrenal insufficiency;
- •clinical or laboratory signs of significant respiratory, hepatobiliary, or pancreatic disease;
- •pregnancy;
- •severe infections, surgery, trauma requiring hospitalization within 3 months before study entry;
- •any active blood or rheumatic disorders, and active liver disease in the previous 5 years;
- •clinically significant chronic kidney disease;
- •severe psychiatric diseases;
- •history of neoplasms in the last 5 years (except for adrenal or pituitary adenoma in Cushing Syndrome, pituitary adenoma or related neolpasms in secondary adrenal insufficiency);
- •heart disease with a class III or class IV functional capacity;
- •BMI greater than 40 kg/m²;
- •use of medication that interferes with cortisol metabolism within 1 month before study entry;
- •treatment with systemic Glucocorticoid (GC) therapy other than hydrocortisone (HC), or cortisone acetate (CA);
- •alcoholism and/or drug addictions;
- •night-shift workers;
- •use of melatonin, antipsychotic medications, estroprogestinic preparations
结局指标
主要结局
Circadian genes CLOCK and ARNTL expression evaluation
时间窗: baseline, +1 month, +3 months, +6 months
Change in relative expression circadian genes of CLOCK and ARNLT from baseline compared to healthy controls. After PBMC isolation by Ficoll-Plaque gradient, complementary DNA (cDNA) pool will be extracted and used as the template for subsequent Polymerase Chain Reaction (PCR) amplification in Real time PCR; Gene expression will be quantified as relative expression compared to housekeeping genes.
次要结局
- Circadian cortisol rhythm(baseline, +1 month, +3 months, +6 months)
- Infectious Diseases Frequency and Severity(baseline, +1 month, +3 months, +6 months)
- Peripheral Blood Mononuclear Cells circadian profiling(baseline, +1 month, +3 months, +6 months)
- Circadian blood pressure(baseline, +1 month, +3 months, +6 months)
- Inflammatory cytokines levels(baseline, +1 month, +3 months, +6 months)
- Quality of life evaluation(baseline, +1 month, +3 months, +6 months)
- Sexual dysfunction in women(baseline, +1 month, +3 months, +6 months)
- Sexual dysfunction in men(baseline, +1 month, +3 months, +6 months)
- Circadian gene expression profile(baseline, +1 month, +3 months, +6 months)
- Sleep Disturbances(baseline, +1 month, +3 months, +6 months)
- Psychometric Evaluation(baseline, +1 month, +3 months, +6 months)
- insuline resistance(baseline, +1 month, +3 months, +6 months)
- blood lipid profile(baseline, +1 month, +3 months, +6 months)
研究者
Andrea M. Isidori
Associate Professor
University of Roma La Sapienza