PegvisOMant and the Immune SystEm (PROMISE)

Acromegaly Clinical Trial

Official title:

The PrOMISE Study: PegvisOMant and the Immune SystEm

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05069324
• Other study ID #: PROMISE
• Status: Completed
• Start date: July 29, 2020
• Est. completion date: June 15, 2023

Study information

• Verified date: July 2023
• Source: University of Roma La Sapienza
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: June 15, 2023
• Est. primary completion date: June 15, 2023
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acromegaly

Locations

Country	Name	City	State
Italy	Department of Experimental Medicine, "Sapienza" University of Rome	Rome

Sponsors (1)

Lead Sponsor	Collaborator
University of Roma La Sapienza

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Peripheral blood mononuclear cell subpopulations	Number of cells (number per mm3) of peripheral blood mononuclear cell subpopulations	baseline
Primary	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	Tumor necrosis factor alfa (TNFa)	Chemiluminescence measurement of TNFa serum concentrations (pg/ml)	baseline and post 8 weeks
Secondary	Transforming growth factor beta (TGF-ß)	Chemiluminescence measurement of TGF-ß serum concentrations (pg/ml)	baseline and post 8 weeks
Secondary	Interleukin-1 (IL-1)	Chemiluminescence measurement of IL-1 serum concentrations (pg/ml)	baseline and post 8 weeks
Secondary	Interleukin-6 (IL-6)	Chemiluminescence measurement of IL-6 serum concentrations (pg/ml)	baseline and post 8 weeks
Secondary	Interleukin-10 (IL-10)	Chemiluminescence measurement of IL-10 serum concentrations (pg/ml)	baseline and post 8 weeks
Secondary	Interferon gamma	Chemiluminescence measurement of interferon gamma serum concentrations (pg/ml)	baseline and post 8 weeks
Secondary	Monocyte chemoattractant protein (MCP-1)	Chemiluminescence measurement of MCP-1 (pg/ml)	baseline and post 8 weeks
Secondary	Adipokines production (visfatin)	Measurement of visfatin serum concentrations	baseline and post 8 weeks
Secondary	Adipokines production (adiponectin)	Measurement of adiponectin serum concentrations	baseline and post 8 weeks
Secondary	Adipokines production (vaspin)	Measurement of vaspin serum concentrations	baseline and post 8 weeks
Secondary	Adipokines production (omentin)	Measurement of omentin serum concentrations	baseline and post 8 weeks
Secondary	Metabolic parameters: glycemia	Evaluation of glucose (mmol/l)	baseline and post 8 weeks
Secondary	Insulin production	Evaluation of insulin (mU/L)	baseline and post 8 weeks
Secondary	Insulin secretion	Evaluation of c-peptide (ng/ml)	baseline and post 8 weeks
Secondary	Metabolic parameters: glycosylated haemoglobin	Evaluation of HbA1c (mmol/mol)	baseline and post 8 weeks
Secondary	Lipid profile: triglycerides	Evaluation of triglycerides (mmol/l)	baseline and post 8 weeks
Secondary	Lipid profile: cholesterol	Evaluation of total cholesterol (mmol/l)	baseline and post 8 weeks
Secondary	Lipid profile: HDL-cholesterol	Evaluation of HDL-cholesterol (mmol/l)	baseline and post 8 weeks
Secondary	Lipid profile: LDL-cholesterol	Evaluation of LDL-cholesterol (mmol/l)	baseline and post 8 weeks
Secondary	Lipid profile: Apo B	Evaluation of apolipoprotein B (mmol/l)	baseline and post 8 weeks
Secondary	Lipid profile: Apo A	Evaluation of apolipoprotein A (mmol/l)	baseline and post 8 weeks
Secondary	Insulin resistance	Evaluation of the homeostasis model assessment for insulin resistance (HOMA-IR) index	baseline and post 8 weeks
Secondary	beta cell function	Evaluation of the homeostasis model assessment for ß cell secretion (HOMA-ß)	baseline and post 8 weeks
Secondary	Body mass index (BMI)	Body weight and height weight will be combined to report BMI in kg/m^2	baseline and post 8 weeks
Secondary	Anthropometric parameters	Waist and hip circumference will be combined to report waist-hip ratio	baseline and post 8 weeks
Secondary	Body composition: lean mass	Lean mass distribution (%) evaluated by a whole-body dual-energy x-ray absorptiometry (DEXA) scan	baseline and post 8 weeks
Secondary	Body composition: fat mass	Fat mass distribution (%) evaluated by a whole-body dual-energy x-ray absorptiometry (DEXA) scan	baseline and post 8 weeks
Secondary	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
Secondary	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
Secondary	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
Secondary	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