Clinical trial NCT05069324: PegvisOMant and the Immune SystEm (PROMISE)
Official title: The PrOMISE Study: PegvisOMant and the Immune SystEm
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acromegaly
Keywords: Acromegaly
Pegvisomant
Immunity
Immune function
Metabolism
Body composition
Quality of life
Sleep disturbances
Lead sponsor: University of Roma La Sapienza
Sponsor class: OTHER
First posted: 2021-10-06
Enrollment: 62
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Peripheral blood mononuclear cell subpopulations
timeFrame: baseline
measure: Change of peripheral blood mononuclear cell subpopulations
timeFrame: baseline and after 8 weeks
Secondary outcomes:
measure: Tumor necrosis factor alfa (TNFα)
timeFrame: baseline and post 8 weeks
measure: Transforming growth factor beta (TGF-β)
timeFrame: baseline and post 8 weeks
measure: Interleukin-1 (IL-1)
timeFrame: baseline and post 8 weeks
measure: Interleukin-6 (IL-6)
timeFrame: baseline and post 8 weeks
measure: Interleukin-10 (IL-10)
timeFrame: baseline and post 8 weeks
measure: Interferon gamma
timeFrame: baseline and post 8 weeks
measure: Monocyte chemoattractant protein (MCP-1)
timeFrame: baseline and post 8 weeks
measure: Adipokines production (visfatin)
timeFrame: baseline and post 8 weeks
measure: Adipokines production (adiponectin)
timeFrame: baseline and post 8 weeks
measure: Adipokines production (vaspin)
timeFrame: baseline and post 8 weeks
measure: Adipokines production (omentin)
timeFrame: baseline and post 8 weeks
measure: Metabolic parameters: glycemia
timeFrame: baseline and post 8 weeks
measure: Insulin production
timeFrame: baseline and post 8 weeks
measure: Insulin secretion
timeFrame: baseline and post 8 weeks
measure: Metabolic parameters: glycosylated haemoglobin
timeFrame: baseline and post 8 weeks
measure: Lipid profile: triglycerides
timeFrame: baseline and post 8 weeks
measure: Lipid profile: cholesterol
timeFrame: baseline and post 8 weeks
measure: Lipid profile: HDL-cholesterol
timeFrame: baseline and post 8 weeks
measure: Lipid profile: LDL-cholesterol
timeFrame: baseline and post 8 weeks
measure: Lipid profile: Apo B
timeFrame: baseline and post 8 weeks
measure: Lipid profile: Apo A
timeFrame: baseline and post 8 weeks
measure: Insulin resistance
timeFrame: baseline and post 8 weeks
measure: beta cell function
timeFrame: baseline and post 8 weeks
measure: Body mass index (BMI)
timeFrame: baseline and post 8 weeks
measure: Anthropometric parameters
timeFrame: baseline and post 8 weeks
measure: Body composition: lean mass
timeFrame: baseline and post 8 weeks
measure: Body composition: fat mass
timeFrame: baseline and post 8 weeks
measure: Biochemical control
timeFrame: baseline and post 8 weeks
measure: Quality of life SF-36-Item Health Survey questionnaire
timeFrame: baseline and post 8 weeks
measure: Acromegaly Quality of Life Questionnaire
timeFrame: baseline and post 8 weeks
measure: Sleep apnea
timeFrame: baseline and post 8 weeks
Other outcomes:
Locations:
city: Rome
country: Italy
facility: Department of Experimental Medicine, "Sapienza" University of Rome
Study officials:
affiliation: Department of Experimental Medicine, "Sapienza" University of Rome
name: Andrea M Isidori, PHD
role: PRINCIPAL_INVESTIGATOR
References: