PegvisOMant and the Immune SystEm (PROMISE)

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.

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.