Somatostatin Analogue Treatment of Acromegaly: Molecular Aspects

The treatment with SA still leaves some questions unanswered. Firstly, SA treatment often results in a concomitant suppression of the insulin secretion, which might lead to clinically significant glucose intolerance. Secondly, the traditional evaluation of disease activity by measuring circulating levels of GH and total IGF-I is not reliable enough

Hypotheses: Treatment of acromegaly with SA versus surgery alone is associated with:

• Glucose intolerance despite normalized insulin sensitivity
• Modified peripheral GH activity in peripheral target organs assessed on molecular endpoints

Study Overview

• Status: Completed
• Conditions: Metabolic Diseases; Acromegaly
• Intervention / Treatment: Drug: genotropin

Detailed Description

Acromegaly is a rare disease usually caused by a benign growth hormone (GH) producing pituitary adenoma. In case of inadequate disease control, the condition is associated with significant morbidity and approximately a doubling of mortality compared to the background population. Medical treatment with somatostatin analogues (SA) has been employed for about 20 years and is a well-established treatment in cases where surgery is impossible or inadequate. The treatment with SA still leaves some questions unanswered. Firstly, SA treatment often results in a concomitant suppression of the insulin secretion, which might lead to clinically significant glucose intolerance. Secondly, the traditional evaluation of disease activity by measuring circulating levels of GH and total IGF-I is not reliable enough

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Aarhus University Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• > 18 years
• treated acromegaly
• considered suitable

Exclusion Criteria:

• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: surgery treated; 10 patients with well-controlled acromegaly for at least 6 months after surgery alone. Stimulated with genotropin	Drug: genotropin; iii) intravenous exogenous bolus of GH (0.5 mg) followed by muscle and fat biopsies.; Other Names: growth hormone
ACTIVE_COMPARATOR: SA treated; 10 patients with well-controlled acromegaly for at least 6 months after SA treatment Stimulated with genotropin	Drug: genotropin; iii) intravenous exogenous bolus of GH (0.5 mg) followed by muscle and fat biopsies.; Other Names: growth hormone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Metabolism - including GH, IGF-I, FFA, glc and insulin. Concentration and AUC (area under the curve)	GH (ug/l), IGF-I (ug/l), FFA (mmol/l) , glc (mmol/l) and insulin (pmol/l)	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
concentration of serum and interstitial GH, bioactive IGF-I as well as total IGF-I	GH (ug/l), IGF-l (ug/l), bioactive IGF-l (ug/l)	3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
GH, and insulin signal transduction in muscle and fat biopsies and regulation of lipolysis.	By western blot technique protien levels of (arbitrary densitomety units) AKT, pAKT threonin, pAKT serine, STAT5, pSTAT5, PTEN, p85alpha, mTOR, pmTOR. By PCR technique (relative nRNA expression) mRNA levels of IGF-1, SOCS1, SOCS2, SOCS3, CISH, PTEN, Pik3r	3 years
patient characterization	sex (M/F), age (year), disease duration (years), BMI (kg/m2)	3 years

Collaborators and Investigators

• Sponsor: University of Aarhus
• Investigators: Study Director: Jens Otto L Joergensen, professor, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (ACTUAL): May 1, 2015
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: November 6, 2012
• First Submitted That Met QC Criteria: November 7, 2012
• First Posted (ESTIMATE): November 8, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): April 5, 2016
• Last Update Submitted That Met QC Criteria: April 4, 2016
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Acromegaly; Somatostatin treatment; metabolic effect
• 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; Metabolic Diseases; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: 1-10-72-491-12; 35197 (OTHER: VEK)

Plan for Individual participant data (IPD)

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