The PrOMISE Study: PegvisOMant and the Immune SystEm
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Change of peripheral blood mononuclear cell subpopulations
Study Overview
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.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Outcomes
Primary Outcomes
Change of peripheral blood mononuclear cell subpopulations
Time Frame: baseline and after 8 weeks
Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations
Peripheral blood mononuclear cell subpopulations
Time Frame: baseline
Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations
Secondary Outcomes
- Adipokines production (vaspin)(baseline and post 8 weeks)
- Tumor necrosis factor alfa (TNFα)(baseline and post 8 weeks)
- Transforming growth factor beta (TGF-β)(baseline and post 8 weeks)
- Interleukin-1 (IL-1)(baseline and post 8 weeks)
- Interleukin-6 (IL-6)(baseline and post 8 weeks)
- Interleukin-10 (IL-10)(baseline and post 8 weeks)
- Monocyte chemoattractant protein (MCP-1)(baseline and post 8 weeks)
- Interferon gamma(baseline and post 8 weeks)
- Adipokines production (omentin)(baseline and post 8 weeks)
- Metabolic parameters: glycemia(baseline and post 8 weeks)
- Insulin production(baseline and post 8 weeks)
- Insulin secretion(baseline and post 8 weeks)
- Lipid profile: triglycerides(baseline and post 8 weeks)
- Lipid profile: HDL-cholesterol(baseline and post 8 weeks)
- Lipid profile: Apo B(baseline and post 8 weeks)
- beta cell function(baseline and post 8 weeks)
- Biochemical control(baseline and post 8 weeks)
- Adipokines production (visfatin)(baseline and post 8 weeks)
- Adipokines production (adiponectin)(baseline and post 8 weeks)
- Lipid profile: cholesterol(baseline and post 8 weeks)
- Lipid profile: LDL-cholesterol(baseline and post 8 weeks)
- Metabolic parameters: glycosylated haemoglobin(baseline and post 8 weeks)
- Lipid profile: Apo A(baseline and post 8 weeks)
- Body composition: lean mass(baseline and post 8 weeks)
- Insulin resistance(baseline and post 8 weeks)
- Body mass index (BMI)(baseline and post 8 weeks)
- Anthropometric parameters(baseline and post 8 weeks)
- Body composition: fat mass(baseline and post 8 weeks)
- Acromegaly Quality of Life Questionnaire(baseline and post 8 weeks)
- Quality of life SF-36-Item Health Survey questionnaire(baseline and post 8 weeks)
- Sleep apnea(baseline and post 8 weeks)
Investigators
Andrea M. Isidori
Full Professor
University of Roma La Sapienza