Bone MicroArchitecture in Acromegaly

Cross-sectional Study of Bone Density, Bone Microarchitecture, Vertebral Fractures and Trabecular Bone Score in Patients With Acromegaly Treated With Pegvisomant Compared to Patients With Untreated Active Acromegaly

The investigators will conduct a cross-sectional study of bone density, bone microarchitecture, vertebral fractures and trabecular bone score in 25 patients with acromegaly treated with Pegvisomant, the growth hormone (GH) receptor antagonist for at least 1 year and with normal insulin-like growth factor-1 (IGF-1) levels. This study aims to describe the bone architecture and associated biochemical indices of bone turnover and metabolism in patients with active acromegaly and how these are altered with treatment of the disease.

Study Overview

• Status: Completed
• Conditions: Acromegaly; Osteoporosis Risk
• Intervention / Treatment: Drug: Pegvisomant

Detailed Description

Growth hormone (GH) and Insulin-Like Growth Factor-1 (IGF-1) are important regulators of bone modeling and remodeling, fundamental to maintenance of normal skeletal integrity. In acromegaly, a disease characterized by longstanding exposure to excess GH and IGF-1, these hormones induce marked skeletal changes. Most dual energy X-ray absorptiometry (DXA) studies report that bone mineral density (BMD) is normal in acromegaly. Despite this, however, there is mounting evidence that bone health is adversely affected in patients with both active and successfully treated acromegaly.

• Study Type: Observational
• Enrollment (Actual): 77

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Neuroendocrine Unit and Pituitary Center, Columbia University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

25 subjects with acromegaly on pegvisomant therapy with a normal IGF-1 level for at least 1 year will be studied.

Patients will be on stable doses of any pituitary hormone supplements for 3 months prior to study entry including gonadal steroid replacement for men or premenopausal women. Hypogonadal men and premenopausal women will be replaced with clinically appropriate sex steroid replacement. Subjects will be 50% females.

Description

Inclusion Criteria:

• Individuals with acromegaly
• On pegvisomant therapy with a normal IGF-1 level for at least 1 year

Exclusion Criteria:

• Malignancy (except cured basal, squamous cell skin carcinoma or other cured cancers free from recurrence > 3 years)
• Pregnancy or lactation within last 12 months
• Untreated primary hyperparathyroidism, hyper- or hypothyroidism
• Cushing's syndrome
• Prolactin-secreting pituitary adenoma
• GH deficiency
• On current drug therapy for osteoporosis
• Diabetes mellitus
• Renal insufficiency
• Liver disease
• Current or past use of glucocorticoids (more than physiologic dose), anticonvulsants, anticoagulants, methotrexate, aromatase inhibitors

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Acromegaly patients on pegvisomant; 25 subjects with acromegaly on pegvisomant therapy with a normal IGF-1 level for at least 1 year.	Drug: Pegvisomant; Subjects receiving pegvisomant as part of their clinical care for acromegaly will be studied.; Other Names: Somavert

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Volumetric bone mineral density of radius (vBMD)	Volumetric bone mineral density of radius (vBMD) measured by high resolution peripheral quantitative computed tomography (HRpQCT)	Measured once at one study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Trabecular number of radius (TbN)	HRpQCT determined bone microarchitecture	Measured once at one study visit
Trabecular Thickness of radius (Tb.Th)	HRpQCT determined bone microarchitecture	Measured once at one study visit
Trabecular separation of radius (Tb.Sp)	HRpQCT determined bone microarchitecture	Measured once at one study visit
Cortical density of radius	HRpQCT determined bone microarchitecture	Measured once at one study visit
Cortical thickness of radius	HRpQCT determined bone microarchitecture	Measured once at one study visit
Areal bone mineral density (aBMD) of lumbar sacral spine	Areal bone mineral density of lumbar sacral spine determined by DXA	Measured once at one study visit
Trabecular bone score of LS spine	Trabecular bone score of lumbar sacral (LS) spine determined by DXA	Measured once at one study visit

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 3, 2016
• Primary Completion (ACTUAL): December 21, 2019
• Study Completion (ACTUAL): December 21, 2019

Study Registration Dates

• First Submitted: July 13, 2017
• First Submitted That Met QC Criteria: July 19, 2017
• First Posted (ACTUAL): July 21, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2021
• Last Update Submitted That Met QC Criteria: July 12, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Acromegaly; Osteoporosis; Pegvisomant
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Endocrine System Diseases; Musculoskeletal Diseases; Hypothalamic Diseases; Bone Diseases; Bone Diseases, Metabolic; Bone Diseases, Endocrine; Hyperpituitarism; Pituitary Diseases; Osteoporosis; Acromegaly
• Other Study ID Numbers: AAAE5304

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No