Brief Title
Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly
Official Title
Impact of Somatostatin Analogs vs. Surgery on Glucose Metabolism in Acromegaly: Results of a 5 Years Observational, Open, Prospective Study
Brief Summary
To investigate the 60 month impact of surgery and somatostatin analogues (SSA) on glucose
metabolism in acromegaly we will analyzed data from 100 patients with acromegaly according
with different treatments (group A=with SSA only; group B= SSA followed by surgery; group C=
surgery only; group D= surgery followed by SSA). At diagnosis and after 6-12 and 60 months
were analyzed as primary outcome measure changes in fasting glucose and as secondary outcome
measures changes of glycated hemoglobin (HbA1c) and insulin levels, HOMA-R and HOMA-β,
representing insulin resistance and β-cell function, respectively.
We will enrol 100 patients and expect half of them to have IGT or diabetes mellitus. We do
not expect changes according with different treatment after 60 months while SSA-treated
patients might experience deterioration of glucose tolerance after 6-12 months. We intend to
look for predictors of deterioration of glucose tolerance.
Detailed Description
Impaired glucose tolerance (IGT) and overt diabetes mellitus are frequently associated with
acromegaly. Patients with acromegaly are insulin resistant both in the liver and in the
periphery, displaying hyperinsulinemia and increased glucose turn-over in the basal
post-absorptive states. The prevalence of diabetes mellitus and that of IGT in acromegaly is
unknown but is reported to range 19-56% and 16-46% in different series. The increased
cardiovascular morbidity and mortality associated with acromegaly may party be a consequence
of the increased insulin resistance that frequently accompanies GH excess. Glucose tolerance
may worsen in patients treated with somatostatin analogues (SSA), because insulin secretion,
i.e. β-cell function, is also suppressed. SSA induce control of GH and IGF-I excess in
approximately 60% of patients after 12 months of treatment with no significant difference as
applied after unsuccessful surgery or as first-line in newly diagnosed patients and control
of GH and IGF-I levels occur with an even higher prevalence after a longer period of
treatment. The inhibitory effect of SSA on pancreatic insulin secretion might, however,
complicate the overall effect of this treatment on glucose tolerance. We recently
demonstrated that 12 months after first-line treatment with SSA or surgery produced a similar
improvement in LV hypertrophy and diastolic filling while systolic function increased more
evidently in SSA-treated patients, total/HDL-cholesterol ratio significantly reduced only in
SSA-treated patients while fasting glucose levels significantly reduced only in
surgery-treated patients. A normal pituitary function was found in 46.4% of SSA-treated and
in 36.4% of surgery-treated patients, resulting unchanged in the former and slightly reduced
in the latter. Both a direct effect of SSA and a more preserved pituitary function might
explain these results. Longitudinal data of glucose tolerance in patients with acromegaly and
with or without diabetes treated long-term with SSA or surgery or both are still very
limited.
In order to investigate whether SSA negatively impact glucose tolerance in acromegaly, we
will analyze data collected prospectively during a 10 year period. We will compare the
results of glucose tolerance at diagnosis after 6-12 months and after 60 months of treatment
with SSA or surgery. Patients will be grouped according with their treatment (SSA only,
surgery only, SSA followed by surgery and SSA followed by surgery and SSA) in order to
establish the effects on glucose tolerance mediated by disease control and type of treatment.
Study Type
Observational
Primary Outcome
Changes of fasting glucose levels.
Secondary Outcome
changes in Hb1Ac levels changes in fasting insulin levels changes in HOMA-R index changes in HOMA-β index
Condition
Acromegaly
Intervention
Octreotide-LAR or lanreotide
Study Arms / Comparison Groups
Group A
Description: >15 patients treated only with SSA (octreotide-LAR or lanreotide depot)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
100
Start Date
January 1997
Completion Date
June 2008
Primary Completion Date
June 2008
Eligibility Criteria
Inclusion Criteria:
- Patients treated with either first-line surgery via trans-sphenoidal route by
microscopic and/or endoscopic approach or with first-line depot SSA treatment, or both
and
- Patients with available follow-up after 60 months of treatment
Exclusion Criteria:
- Patients requiring dopamine-agonists or pegvisomant
- Patients receiving the s.c. octreotide for longer than 15 days
- Patients receiving radiotherapy,
- Patients with a follow-up shorter than 60 months
Gender
All
Ages
18 Years - 80 Years
Accepts Healthy Volunteers
No
Contacts
Annamaria Colao, MD, ,
Location Countries
Italy
Location Countries
Italy
Administrative Informations
NCT ID
NCT00703079
Organization ID
NeuroendoUnit-10
Study Sponsor
Federico II University
Study Sponsor
Annamaria Colao, MD, Principal Investigator, Federico II University
Verification Date
June 2008