Glucose Tolerance in Acromegaly: The Influence of GH-excess on Glucose Metabolism and Insulin Resistance
Condition: Acromegaly; Diabetes; Insulin Resistance; Impaired Glucose Tolerance
MeSH terms: Acromegaly; Insulin Resistance; Glucose Intolerance
Study type: Observational

Summary: 
      Observational, Cross-sectional, longitudinal, multi-center, diagnostic study

      Cross-sectional part of the study: To evaluate the influence of acromegaly on glucose
      tolerance

      Longitudinal part of the study: To evaluate the changes of impaired glucose tolerance during
      standard treatment of acromegaly. Adult patients with established acromegaly

      Cross-sectional part of the study: 150 patients

      Longitudinal part of the study: 58 patients
    

Detailed description: 
      TRIAL DESIGN Observational, cross-sectional (patients with normal glucose tolerance).
      longitudinal (patients with impaired glucose tolerance), multi-center, diagnostic study.

      After checking the inclusion and exclusion criteria for the cross-sectional part of the study
      patients will be included for anamnesis according to Flow Chart Visit -1 (Screening Visit).
      After checking the glucose tolerance and the insulin resistance by HOMA-IR, the patients will
      be classified to the group with normal glucose tolerance defined as:

        -  fasting plasma glucose < 110 mg/dl and/or 2-hour plasma glucose after an OGTT < 140
           mg/dl or to the group with impaired glucose tolerance defined as:

             -  fasting plasma glucose ≥ 110 mg/dl (IFG) and/or 2-hour plasma glucose after an OGTT
                ≥ 140 mg/dl (IGT). For the HOMA-IR the cut off is 1.5.

      For patients with normal glucose tolerance the study will end after Screening Visit (V -1).

      After patient recruitment of the cross-sectional part is completed an interim analysis is
      planned to verify that all criteria for the longitudinal study part are achieved. The
      longitudinal part should start not later than one year after the last patient was examined in
      the cross-sectional part. For patients with impaired glucose tolerance the inclusion and
      exclusion criteria for the longitudinal part of the study will be checked (Baseline, Visit
      0). If a patient might be included into the longitudinal part of the study a 12 months
      observation with 4 further visits will follow.

      Primary Objective and Endpoint

      Cross-sectional part of the study:

      To evaluate a correlation between IGF-I and glucose tolerance in acromegalic patients. The
      inclusion should be performed in 2 stratification groups.

      Following two groups are defined:

        1. 1/3 of patients with a controlled IGF-I (controlled means IGF-I in age and sex-related
           normal reference range.

        2. 2/3 of patients with an uncontrolled IGF-I (uncontrolled means IGF-I not in age and sex
           related normal reference range.

      Longitudinal part of the study:

      To evaluate changes of impaired glucose tolerance by different standard treatment options in
      acromegaly.

      For the analysis of the different treatment options patients will be stratified into 5
      treatment groups. Decision will be made according to next planned therapeutic intervention at
      Screening Visit (V -1):

        1. Surgery

        2. Treatment with somatostatin analoga (with or without combination of dopamine agonists)

        3. Treatment with growth hormone receptor antagonist

        4. Treatment with somatostatin analoga in combination with growth hormone receptor
           antagonist

        5. Others (e.g. radiation, dopamine agonist monotherapy, no intervention)
    

Observational model: Case-Only
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        1. Acromegaly in adult subjects (≥ 18 years) either controlled or uncontrolled (Diagnosis
             should be based on OGTT where Acromegaly is defined as a lack of suppression of GH
             nadir to < 0.5 ng/dL, after oral administration of 75 g of glucose, OGTT and IGF-I
             levels at least 10 % above the normal value ± 2 SD).

          2. Written informed consent
      
Biospecimen description: 
      serum
    
Keywords: acromegaly; diabetes; insulin resistance; impaired glucose tolerance