Cardiac (CMRI) Assessment of Acromegaly (ACROCOEUR)

Cardiac Structure and Function in Acromegalic Patients: A Cardiac Magnetic Resonance Imaging Study

In this study, the investigators will evaluate the cardiac structure and function, focusing on the myocardial water content and interstitial fibrosis, in patients with active acromegaly in comparison with 1) healthy volunteers, 2) the same acromegalic patients that have received efficient therapy.

The investigators hypothesize that the myocardial water content in acromegaly is increased as these patients present with sodium and water retention and that this myocardial water infiltration will improve with efficient treatment of the disease. They will thus assess using CMRI, this parameter by measuring the myocardial transverse relaxation time (T2), reflecting water content in the myocardium.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Device: CMRI; Drug: Gadolinium; Procedure: OGTT

Detailed Description

Patients with acromegaly have left ventricular (LV) hypertrophy and dysfunction on echocardiography, but only very few studies have been performed using cardiac magnetic resonance imaging (CMRI), currently the reference modality is assessment in cardiac geometry function. In addition, no data are available on right ventricular (RV) and atrial structure and function. The pathophysiology of the cardiac involvement in acromegaly may be related to increase myocardiac water content and/or interstitial myocardiac fibrosis.

The main objective of sthe study is to compare the myocardial water content in patients with acromegaly and in healthy volunteers. Secondary objectives of the study are to evaluate :

1. interstitial fibrosis and the structure and the function of LV and RV in acromegalic patients in comparison with healthy volunteers;
2. the reversibility of the cardiac involvement (water content, fibrosis, LV and RV structure and function) after efficient treatment of acromegaly;
3. the elasticity of aorta in acromegalic patients in comparison with healthy volunteers and with the post-treatment state. Twenty acromegalic patients will be included in order to dispose of 15 patients that will completed the study and the same number of age- and BMI-adjusted healthy volunteers will be included.

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94275
    • AP-HP, Bicêtre Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active acromegaly as defined by the usual diagnostic criteria (de novo patients or patients uncontrolled by previous treatments).
• Healthy volunteers matched for age, sex and BMI with the patients of the group 1

Exclusion Criteria:

• History of coronary heart disease (acute or chronic myocardial ischemia)
• Acute or chronic renal failure (creatinin clearance 30 mL/min/l,73m2)
• Contraindication of MRI
• Hypersensitivity to gadolinium
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: OGTT, CMRI with gadolinium in patients; Patients with acromegaly will be investigated	Device: CMRI; Myocardial Imaging (CMRI) will be performed in patients (at baseline and 6 month after treatment) and healthy volunteers (baseline); Drug: Gadolinium; gadolinium injection will be performed during CMRI in patients and healthy volunteers.; Other Names: Gadolinium injection; Procedure: OGTT; Growth Hormon (GH) secretion and metabolic status of the acromegalic will be evaluated by an measure of plasma glucose, insulin and GH (OGTT), and insulin-like growth factor-1 (IGF-I) will be measured in patients and healthy volunteers.
ACTIVE_COMPARATOR: OGTT, CMRI with gadolinium in volunteers; Age-, sex- and BMI-matched healthy volunteers will be investigated	Device: CMRI; Myocardial Imaging (CMRI) will be performed in patients (at baseline and 6 month after treatment) and healthy volunteers (baseline); Drug: Gadolinium; gadolinium injection will be performed during CMRI in patients and healthy volunteers.; Other Names: Gadolinium injection; Procedure: OGTT; Growth Hormon (GH) secretion and metabolic status of the acromegalic will be evaluated by an measure of plasma glucose, insulin and GH (OGTT), and insulin-like growth factor-1 (IGF-I) will be measured in patients and healthy volunteers.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Myocardial transverse relaxation time (T2), reflecting water content assessed by CMRI	This outcome will be compared between patients and healthy volunteers.	Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Change from baseline Myocardial transverse relaxation time (T2) at 6 months, reflecting water content assessed by CMRI		Baseline and 6 months after beginning of the treatment in acromegalic patients

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dense myocardial fibrosis	The dense myocardial fibrosis will be depicted by late gadolinium enhancement.	Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Interstitial myocardial fibrosis	Interstitial myocardial fibrosis will be quantified by T1 measurements before and after gadolinium injection.	Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Cardiac morphology will also be assessed CMRI		Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Function including Left Ventricular mass index will also be assessed CMRI		Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Function including Left Auricular ejection fractions will also be assessed CMRI		Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Function including Left Ventricular ejection fractions will also be assessed CMRI		Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Function including Right Ventricular ejection fractions will also be assessed CMRI		Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Function including Left Ventricular and Right Ventricular stroke volumes will also be assessed CMRI		Baseline in acromegalic patients; at the 1 day evaluation visit in healthy volunteers
Change from baseline Dense myocardial fibrosis at 6 months	"The dense myocardial fibrosis will be depicted by late gadolinium enhancement.	Baseline and 6 months after beginning of the treatment in acromegalic patients
Change from baseline interstitial myocardial fibrosis at 6 months		Baseline and 6 months after beginning of the treatment in acromegalic patients

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Pfizer
• Investigators: Principal Investigator: Philippe CHANSON, MD, PhDI, AP-HP, Bicêtre Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ACTUAL): June 9, 2017
• Study Completion (ACTUAL): February 28, 2019

Study Registration Dates

• First Submitted: December 8, 2015
• First Submitted That Met QC Criteria: October 26, 2016
• First Posted (ESTIMATE): October 28, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 14, 2019
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: left ventricular dysfunction; left ventricular hypertrophy; myocardial fibrosis; Acromegaly,; water retention
• 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: P121004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO