PegvisOMant and the Immune SystEm (PROMISE)
- Conditions
- Acromegaly
- Registration Number
- NCT05069324
- Lead Sponsor
- University of Roma La Sapienza
- Brief Summary
This is a prospective observational pilot study for the evaluation of immune cells phenotype in acromegalic patients in comparison with a control population and to investigate the impact of disease control and different medical treatments (particularly Pegvisomant) on immune function and its implication on insulin resistance, metabolic complications and fat accumulation.
- Detailed Description
The observational study will concern the collection of data from patients who, as they are not controlled by SSAs therapy (cohort 1), require PEG therapy in monotherapy (group 1) or in combination with SSAs (group 2), according to common clinical practice. The investigators will enroll also acromegalic patients adequately controlled by medical therapy (cohort 2), respectively treated by any kind of SSAs (group 3) and by PEG (group 4) for comparison between different medical treatments. The data will be prospectively collected at baseline and after 8 weeks of treatment.
A control group will be enrolled including healthy volunteers matched with patients for age and sex.
The primary outcome will be the immune profiling by quantification of peripheral blood mononuclear cells (PBMC) subpopulations.
Secondary outcome measures will be
* Evaluation of inflammatory cytokines and adipokines production.
* Evaluation of glucose, insulin, c-peptide, HbA1c, triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol apolipoprotein B and A. Insulin resistance and β cell function will be assessed by the homeostasis model assessment for insulin resistance (HOMA-IR) index and for β cell secretion (HOMA-β). Anthropometric measurements will include body weight, height and waist and hip circumference.
* Evaluation of body composition. Composite outcome measure consisting of lean mass, skeletal muscle and fat distribution analysis.
* Fasting samples from all patients will be assayed for disease control parameters.
* Evaluation of quality of life. Quality of life will be measured by Short Form (SF)-36-Item Health Survey total score, SF-36-Item Health Survey physical component summary score and SF-36-Item Health Survey mental component summary score and Acromegaly quality of life (AcroQol) questionnaire.
* Evaluation of sleep disturbances. Sleep disturbances will be measured by Epworth Sleepiness Scale (ESS) and by polysomnography when appropriate.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 62
- Previously diagnosed acromegaly not adequately controlled by surgery and/or radiation therapy and in whom an appropriate medical treatment with any kind of somatostatin analogs (SSAs) did not control the disease or was not tolerated;
- Previously diagnosed acromegaly adequately controlled by medical treatment;
- Signed informed consent to participate in the study.
- Adequately controlled disease by surgery and/or radiation;
- Patients with transaminases more than 3 times the upper limit of normal;
- Hypersensitivity to PEG or any of its ingredients;
- History of other neoplasms, radiotherapy or chemotherapy in the last 5 years;
- Clinical or laboratory signs of significant hepatobiliary, or pancreatic disease;
- Severe infections, surgery, trauma requiring hospitalization within 3 months before enrolment;
- Severe chronic kidney disease (stage 4-5);
- Any active blood or rheumatic disorders in the last 5 years;
- Pregnant or nursing women.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Change of peripheral blood mononuclear cell subpopulations baseline and after 8 weeks Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations
Peripheral blood mononuclear cell subpopulations baseline Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations
- Secondary Outcome Measures
Name Time Method Adipokines production (vaspin) baseline and post 8 weeks Measurement of vaspin serum concentrations
Tumor necrosis factor alfa (TNFα) baseline and post 8 weeks Chemiluminescence measurement of TNFα serum concentrations (pg/ml)
Transforming growth factor beta (TGF-β) baseline and post 8 weeks Chemiluminescence measurement of TGF-β serum concentrations (pg/ml)
Interleukin-1 (IL-1) baseline and post 8 weeks Chemiluminescence measurement of IL-1 serum concentrations (pg/ml)
Interleukin-6 (IL-6) baseline and post 8 weeks Chemiluminescence measurement of IL-6 serum concentrations (pg/ml)
Interleukin-10 (IL-10) baseline and post 8 weeks Chemiluminescence measurement of IL-10 serum concentrations (pg/ml)
Monocyte chemoattractant protein (MCP-1) baseline and post 8 weeks Chemiluminescence measurement of MCP-1 (pg/ml)
Interferon gamma baseline and post 8 weeks Chemiluminescence measurement of interferon gamma serum concentrations (pg/ml)
Adipokines production (omentin) baseline and post 8 weeks Measurement of omentin serum concentrations
Metabolic parameters: glycemia baseline and post 8 weeks Evaluation of glucose (mmol/l)
Insulin production baseline and post 8 weeks Evaluation of insulin (mU/L)
Insulin secretion baseline and post 8 weeks Evaluation of c-peptide (ng/ml)
Lipid profile: triglycerides baseline and post 8 weeks Evaluation of triglycerides (mmol/l)
Lipid profile: HDL-cholesterol baseline and post 8 weeks Evaluation of HDL-cholesterol (mmol/l)
Lipid profile: Apo B baseline and post 8 weeks Evaluation of apolipoprotein B (mmol/l)
beta cell function baseline and post 8 weeks Evaluation of the homeostasis model assessment for β cell secretion (HOMA-β)
Biochemical control baseline and post 8 weeks Fasting samples from all patients will be assayed for disease control parameters (insulin-growth factor and growth hormone)
Adipokines production (visfatin) baseline and post 8 weeks Measurement of visfatin serum concentrations
Adipokines production (adiponectin) baseline and post 8 weeks Measurement of adiponectin serum concentrations
Lipid profile: cholesterol baseline and post 8 weeks Evaluation of total cholesterol (mmol/l)
Lipid profile: LDL-cholesterol baseline and post 8 weeks Evaluation of LDL-cholesterol (mmol/l)
Metabolic parameters: glycosylated haemoglobin baseline and post 8 weeks Evaluation of HbA1c (mmol/mol)
Lipid profile: Apo A baseline and post 8 weeks Evaluation of apolipoprotein A (mmol/l)
Body composition: lean mass baseline and post 8 weeks Lean mass distribution (%) evaluated by a whole-body dual-energy x-ray absorptiometry (DEXA) scan
Insulin resistance baseline and post 8 weeks Evaluation of the homeostasis model assessment for insulin resistance (HOMA-IR) index
Body mass index (BMI) baseline and post 8 weeks Body weight and height weight will be combined to report BMI in kg/m\^2
Anthropometric parameters baseline and post 8 weeks Waist and hip circumference will be combined to report waist-hip ratio
Body composition: fat mass baseline and post 8 weeks Fat mass distribution (%) evaluated by a whole-body dual-energy x-ray absorptiometry (DEXA) scan
Acromegaly Quality of Life Questionnaire baseline and post 8 weeks Evaluation of quality of life by the Acromegaly Quality of Life Questionnaire (ACROQOL), a disease specific questionnaire to measure quality of life in patients with acromegaly. It contains 22 items divided in two scales that measure physical and psychological aspects. Each of the 22 items of the AcroQoL is answered in a 1 to 5. A global score is obtained adding the results of the 22 items using a specific formula, from a minimum of 22 - worse QoL - until 110 - best QoL -
Quality of life SF-36-Item Health Survey questionnaire baseline and post 8 weeks Quality of life will be evaluated by the Physical Component score and the Mental Component score of the self administered questionnaire SF-36-Item Health Survey questionnaire.
This questionnaire measures eight scales: physical functioning, role physical, bodily pain, general health (physical component) and vitality, social functioning, role emotional, mental health (mental component).
Interpretation of the score will be the following: at each item of the questionnaire corresponds a percentage value (from 0% to 100%). The average of the single items constitutes the scale total percentage (from 0% to 100%); missing data are not considered during calculation. High score defines a more favorable health stateSleep apnea baseline and post 8 weeks Sleep disturbances will be measured by Epworth Sleepiness Scale (ESS). The ESS consists of eight questions regarding eight activities. Each of the activities listed has an assigned score from 0 to 3 that indicates how likely a person is to fall asleep during the activity:
0 = would never doze, 1 = slight chance of dozing, 2 = moderate chance of dozing, 3 = high chance of dozing.
The total score can range from 0 to 24. A higher score is associated with increased sleepiness.
Trial Locations
- Locations (1)
Department of Experimental Medicine, "Sapienza" University of Rome
🇮🇹Rome, Italy