PegvisOMant and the Immune SystEm (PROMISE)

The PrOMISE Study: PegvisOMant and the Immune SystEm

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.

Study Overview

• Status: Completed
• Conditions: Acromegaly

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 Type: Observational
• Enrollment (Actual): 62

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00161
    • Department of Experimental Medicine, "Sapienza" University of Rome

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

10 patients with acromegaly not well controlled by SSAs therapy (cohort 1), requiring add PEG to SSAs or switch to PEG monotherapy, according to common clinical practice.

20 patients adequately controlled by medical therapy (cohort 2), treated by any kind of SSAs or by PEG .

30 age- and sex matched controls.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Acromegaly patients not adequately controlled by any kind of SSAs monotherapy; Acromegaly patients not adequately controlled by any kind of SSAs monotherapy, requiring PEG in combination with SSAs or PEG monotherapy
Acromegaly patients adequately controlled by medical treatment; Acromegaly patients adequately controlled by medical treatment, by any kind of SSAs or by PEG
Healthy controls; Healthy volunteers matched with patients for age and sex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peripheral blood mononuclear cell subpopulations	Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations	baseline
Change of peripheral blood mononuclear cell subpopulations	Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations	baseline and after 8 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor necrosis factor alfa (TNFα)	Chemiluminescence measurement of TNFα serum concentrations (pg/ml)	baseline and post 8 weeks
Transforming growth factor beta (TGF-β)	Chemiluminescence measurement of TGF-β serum concentrations (pg/ml)	baseline and post 8 weeks
Interleukin-1 (IL-1)	Chemiluminescence measurement of IL-1 serum concentrations (pg/ml)	baseline and post 8 weeks
Interleukin-6 (IL-6)	Chemiluminescence measurement of IL-6 serum concentrations (pg/ml)	baseline and post 8 weeks
Interleukin-10 (IL-10)	Chemiluminescence measurement of IL-10 serum concentrations (pg/ml)	baseline and post 8 weeks
Interferon gamma	Chemiluminescence measurement of interferon gamma serum concentrations (pg/ml)	baseline and post 8 weeks
Monocyte chemoattractant protein (MCP-1)	Chemiluminescence measurement of MCP-1 (pg/ml)	baseline and post 8 weeks
Adipokines production (visfatin)	Measurement of visfatin serum concentrations	baseline and post 8 weeks
Adipokines production (adiponectin)	Measurement of adiponectin serum concentrations	baseline and post 8 weeks
Adipokines production (vaspin)	Measurement of vaspin serum concentrations	baseline and post 8 weeks
Adipokines production (omentin)	Measurement of omentin serum concentrations	baseline and post 8 weeks
Metabolic parameters: glycemia	Evaluation of glucose (mmol/l)	baseline and post 8 weeks
Insulin production	Evaluation of insulin (mU/L)	baseline and post 8 weeks
Insulin secretion	Evaluation of c-peptide (ng/ml)	baseline and post 8 weeks
Metabolic parameters: glycosylated haemoglobin	Evaluation of HbA1c (mmol/mol)	baseline and post 8 weeks
Lipid profile: triglycerides	Evaluation of triglycerides (mmol/l)	baseline and post 8 weeks
Lipid profile: cholesterol	Evaluation of total cholesterol (mmol/l)	baseline and post 8 weeks
Lipid profile: HDL-cholesterol	Evaluation of HDL-cholesterol (mmol/l)	baseline and post 8 weeks
Lipid profile: LDL-cholesterol	Evaluation of LDL-cholesterol (mmol/l)	baseline and post 8 weeks
Lipid profile: Apo B	Evaluation of apolipoprotein B (mmol/l)	baseline and post 8 weeks
Lipid profile: Apo A	Evaluation of apolipoprotein A (mmol/l)	baseline and post 8 weeks
Insulin resistance	Evaluation of the homeostasis model assessment for insulin resistance (HOMA-IR) index	baseline and post 8 weeks
beta cell function	Evaluation of the homeostasis model assessment for β cell secretion (HOMA-β)	baseline and post 8 weeks
Body mass index (BMI)	Body weight and height weight will be combined to report BMI in kg/m^2	baseline and post 8 weeks
Anthropometric parameters	Waist and hip circumference will be combined to report waist-hip ratio	baseline and post 8 weeks
Body composition: lean mass	Lean mass distribution (%) evaluated by a whole-body dual-energy x-ray absorptiometry (DEXA) scan	baseline and post 8 weeks
Body composition: fat mass	Fat mass distribution (%) evaluated by a whole-body dual-energy x-ray absorptiometry (DEXA) scan	baseline and post 8 weeks
Biochemical control	Fasting samples from all patients will be assayed for disease control parameters (insulin-growth factor and growth hormone)	baseline and post 8 weeks
Quality of life SF-36-Item Health Survey questionnaire	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 state	baseline and post 8 weeks
Acromegaly Quality of Life Questionnaire	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 -	baseline and post 8 weeks
Sleep apnea	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.	baseline and post 8 weeks

Collaborators and Investigators

• Sponsor: University of Roma La Sapienza
• Investigators: Principal Investigator: Andrea M Isidori, PHD, Department of Experimental Medicine, "Sapienza" University of Rome

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Actual): June 15, 2023
• Study Completion (Actual): June 15, 2023

Study Registration Dates

• First Submitted: October 19, 2020
• First Submitted That Met QC Criteria: October 5, 2021
• First Posted (Actual): October 6, 2021

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 5, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Quality of life; Acromegaly; Body composition; Immunity; Pegvisomant; Metabolism; Sleep disturbances; Immune function
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Acromegaly
• Other Study ID Numbers: PROMISE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No