Effects of Sandostatin LAR® in Acromegaly

Metabolic, Cardiovascular and Body Composition Effects of Sandostatin LAR® Therapy of Acromegaly, Effect of Reduction of Serum Insulin-like Growth Factor 1 (IGF-1) Levels Into a New Normative Range

This study aims primarily to determine the effect Insulin-like Growth Factor 1 (IGF-1) normalization into current IGF-I normal ranges with Sandostatin LAR® therapy on biochemical metabolic, cardiovascular and body composition parameters in patients with active acromegaly.

Study Overview

• Status: Completed
• Conditions: Acromegaly
• Intervention / Treatment: Drug: Sandostatin LAR

Detailed Description

A major goal of treatment of acromegaly is to normalize serum IGF-1 levels. Recently developed new normative data for serum IGF-1 levels has lowered the upper limit of normal for this hormone level. Octreotide, an analog of somatostatin, a synthetic form of the hypothalamic hormone somatostatin, which inhibits growth hormone (GH) release by blocking somatostatin receptors in the pituitary and on the tumor, is now available in a long acting depot formulation, Sandostatin LAR, that suppresses tumoral GH secretion and normalizes GH and IGF-1 levels in about 60% of patients. Although sandostatin LAR is Food and Drug Administration (FDA) approved for the therapy of acromegaly and is used clinically, its efficacy with respect to new normative IGF-1 ranges has not been studied. In addition, an important goal of therapy of acromegaly is to treat co-morbidities of the disease such as insulin resistance, which is common in acromegaly. Other important morbidities in acromegaly are hypertension and cardiovascular disease such as left ventricular hypertrophy (LVH). In this study the investigators will assess the effect of LAR therapy on biochemical parameters as well as important clinical endpoints of therapy of acromegaly.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Adults (age > 18 years) with diagnosis of Acromegaly ( previously confirmed by an elevated IGF-1 level)
2. IGF-1 concentrations> 10% above the upper limit of normal at screening
3. If the patient have undergone surgical resection of a pituitary adenoma, A minimum of two months must have elapsed post surgery prior to enrollment
4. May have a history of radiotherapy
5. Stable pituitary hormone supplements(x months) prior to baseline visit

6. if female ,

   1. not pregnant (as evidence by negative serum pregnancy test) or lactating; and
   2. If childbearing potential, agree to use a medically acceptable form of contraception (such as oral, implantable, or barrier contraception) from the screening, for the duration of the study, and for at least on month after study discontinuation or completion. Childbearing potential is defined as women who are not surgically sterile or not at least one year postmenopausal.
7. Sign and date an consent form document indicating that the subject (or legally acceptable representative) has been informed of and agrees to all pertinent aspects of trial

Exclusion Criteria:

1. Have other conditions that may result in abnormal growth hormone (GH) and/or IGF-1 concentrations (e.g., severe hepatic disease, severe renal disease Malnutrition, treatment with levodopa)
2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x Upper limit of normal or clinically significant hepatic disease
3. Prior somatostatin analog therapy within 6 months of the screening visit
4. Other medical therapy for acromegaly for 6 weeks to screening visit
5. Visual field defects or other neurological symptoms due to tumor mass
6. Have known or suspected drug or alcohol abuse
7. Have received an investigational medication within four week prior to screening or is scheduled to received any investigational medication during the study
8. Do not have ability to fully comprehend the nature of the study, to follow instructions, cooperate with study procedures, and/or are unable to adhere to the visit scheduled outlined in the protocol
9. Have other severe acute or chronic medical or psychiatry condition or Laboratory abnormality that may increase the risk associated with study Participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study
10. Patient who have known hypersensitivity to Sandostatin acetate or other related drug or compound
11. Patient with current gallstones
12. Patient who have received supraphysiologic doses of glucocorticoid within the past 6 months (except for peri-operative (<3 days duration) of dexamethasone) or who currently received chemotherapeutics agents, or exogenous growth hormone
13. Patients who have received other investigational drugs administered or Received within 30 days of study entry
14. Patients who exhibit symptoms indicative of intolerance during the 2 weeks Course of Sandostatin injection.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sandostatin LAR; Nine months of open label dose escalation Sandostatin LAR therapy.	Drug: Sandostatin LAR; Open label dose escalation of Sandostatin LAR 10 mg, 20 mg, 30 mg, up to 40 mg if necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IGF-1 Level on Sandostatin LAR	Mean IGF-1 level on treatment with Sandostatin LAR in whole population and responders (normal IGF1) and non responders(elevated IGF-1)	Up to 9 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiovascular Risk Markers on Sandostatin LAR: C-reactive Protein (CRP) Levels	Levels of C-reactive protein (CRP) in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome.	Up to 9 months
Cardiovascular Risk Markers on Sandostatin LAR: Homocysteine Levels	Levels of homocysteine in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome.	Up to 9 months
Cardiovascular Risk Markers on Sandostatin LAR: Lipid Levels	Levels of lipid panel (cholesterol, triglycerides, and Lipoprotein A) in whole study group, responders (normal IGF-1) and non responders (elevated IGF-1) groups. Higher values are a worse outcome.	Up to 9 months

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Novartis
• Investigators: Principal Investigator: Pamela U Freda, MD, Columbia University

Study record dates

Study Major Dates

• Study Start: October 1, 2006
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: August 19, 2011
• First Submitted That Met QC Criteria: August 25, 2011
• First Posted (Estimated): August 26, 2011

Study Record Updates

• Last Update Posted (Actual): July 24, 2024
• Last Update Submitted That Met QC Criteria: July 22, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Sandostatin LAR
• 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; Antineoplastic Agents; Gastrointestinal Agents; Antineoplastic Agents, Hormonal; Octreotide
• Other Study ID Numbers: AAAC0246; CSMS995BUS57 (Other Grant/Funding Number: Novartis Pharmaceutical, Inc./Investigator Initiated study)

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