- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04066569
Reproducibility and Utility of OGTT in Acromegaly (ACROTEST)
Reproducibility and Utility of Growth Hormone Inhibition by Oral Glucose Tolerance Test for the Diagnosis of Acromegaly
Study Overview
Status
Conditions
Detailed Description
Rational: The initial step of biological diagnosis of acromegaly is based on assessment of IGF-I. According to current recommendations, the diagnosis must be confirmed by an oral glucose tolerance test (OGTT) to show that there is no growth hormone (GH) decrease lower than 1 μg/L (Katznelson , et al., 2014).
Reproducibility of GH suppression by the OGTT has never been evaluated in either acromegalic or healthy subjects, although it is essential to determine the reliability of this test. Spontaneous fluctuations in GH in acromegaly could significantly influence the response of GH to the OGTT and cause low reproducibility of the test in this population. In particular, this reliability could be different according to the typical or moderate clinical presentation because of the persistence of a residual ultradian rhythm of GH secretion.
The usefulness of oral glucose loading and the resulting hyperglycemia (which may limit GH secretion) has never been compared to an appropriate placebo (aspartame, at a dose equivalent to 75 g glucose), which does not cause hyperglycemia. Ingestion of 75 g of glucose is often responsible for nausea and vomiting. More rarely, the drop in blood glucose reactive to hyper insulinemia at the end of the test, can be the cause of discomfort.
Primary objective: To determine the reproducibility of the GH response to OGTT in acromegaly by studying, in subjects with acromegaly, changes in GH concentration within 2 hours after oral administration of 75 g of glucose at 2 repeated tests in the same subject.
Secondary objectives:
- To analyze the reproducibility of the GH response to the OGTT as a function of the severity of acromegaly ("typical" form, "intermediate" form of acromegaly) and in a group of non-acromegalic subjects.
- To evaluate the diagnostic value (utility) of OGTT in acromegaly by comparing, in subjects with acromegaly, the response of GH to oral administration of 75 g of glucose (OGTT) and 375 mg of aspartame (placebo).
- Evaluate OGTT-stimulated insulin secretion in acromegalic and non-acromegalic subjects.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: SALENAVE Sylvie, Dr
- Phone Number: 01 45 21 33 98
- Email: sylvie.salenave@aphp.fr
Study Contact Backup
- Name: KAMENICKY Peter, Dr
- Phone Number: 01 45 87 37 06
- Email: peter.kamenicky@aphp.fr
Study Locations
-
-
-
Le Kremlin-Bicêtre, France, 94275
- AP-HP, Bicêtre Hospital
-
Contact:
- KAMENICKY Peter, Dr
- Phone Number: 01 45 87 37 06
- Email: peter.kamenicky@aphp.fr
-
Contact:
- SALENAVE Sylvie, Dr
- Phone Number: 01 45 21 33 98
- Email: sylvie.salnave@aphp.fr
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Acromegalic subjects
Men or women, adults ≤ 85 years, with hypersecretion of GH proven by the following criteria:
- High IGF-I compared to age and sex standards (Variety study, Chanson et al., 2016)
- and basal GH concentrations > 0.4 μg / L (Katznelson, et al., 2014) and somatotropic pituitary adenoma operated on or planned to be operated on. It may be patients whose acromegaly has just been discovered and not yet treated (de novo patients) for whom a surgical treatment is envisaged within 6 months after inclusion or acromegalic patients already operated on a pituitary adenoma whose acromegaly is not controlled by surgery. A histological confirmation of a somatotropic pituitary adenoma will be obtained either before inclusion in the study (subjects already operated) or after inclusion ("de novo" subjects) in order to have a sufficient level of proof of the diagnosis of acromegaly, especially in the "intermediate" forms.
- Medically treated patients who decide to discontinue treatment (in order to reassess the progression of the disease, or at the time of a change), will be eligible after more than 3 months of discontinuation of the drug treatment.
- In women on estrogen / progestin contraception, this should be kept unchanged throughout the study. In the absence of estrogen / progestin contraception, exploration will be done in the follicular phase.
Non-acromegalic subjects:
- Men or women, adults ≤ 85 years
- Subjects defined by a concentration of IGF-I below 100% of the upper limit of normal, matched for sex and age (± 5 years) to acromegalic patients.
- Normal blood pressure measured by an electronic tensiometer validated after 5 min resting in supine position <140/90 mmHg on 3 consecutive measurements
- Biological assessment (hematological and biochemical blood tests, urine analysis) within the limits of normal or clinically acceptable. Normal EKG.
- ECG 12 leads without particularity.
- Affiliation to a social security scheme
- At the women on estrogen-progestative contraception, this one should be kept unchanged throughout the study. In the absence of estrogen-progestative contraception,the exploration will be done in the follicular phase.
- Signed informed consent.
Exclusion Criteria:
For both groups:
- Pregnant or breastfeeding women
- Acute systemic diseases
- Pathologies likely to affect digestive absorption
- Taking prohibited treatments (see section 7.3)
- History of hypersensitivity to aspartame (edema of Quincke, Urticaria ..)
- Donation of blood in the 3 months preceding the study
- People in the exclusion period on the national file people suitable for research involving the human person
- Refusal or linguistic or psychic incapacity to sign informed consent
- Subject unable to submit to the constraints of the protocol (for example, non-cooperating, unable to return to follow-up visits and probably unable to finish the study)
- Major under guardianship
- Major under curatorship
- People with phenylketonuria
- Person with digestive intolerance to glucose /galactose, digestive labsorption syndrome of glucose / galactose.
For the group of acromegalic patients:
- acromegalic patients with diabetes mellitus treated with insulin
- Acromegalic patients under medical treatment of their acromegaly somatostatin analogues, pegvisomant), or patients in whom this treatment has been suspended for less than 3 months at the time of the selection.
- Acromegalic patients who have been treated with radiotherapy.
For the group of non-acromegalic subjects:
- Chronic systemic diseases likely to influence the secretion of GH like diabetes sweetness, severe obesity (BMI> 35 kg / m2), inadequate renal (creatinine clearance <60 mL / min), disease hypothalamic-pituitary, epilepsy, antecedents Hepatocellular insufficiency and insufficiency cardiac, progressive cancer.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: OGTT Tests and Placebo Test
Patients with acromegaly
|
After inclusion, the study will include the sequential realization of 3 dynamic GH secretion tests, separated by a period of 24 hours to 30 days. Each subject will have two OGTT tests (oral administration of 75 g of glucose in 100 mL of water) and a placebo test (oral administration of 375 mg of aspartame in 100 mL of water). The order of the three tests (2 OGTT and 1 placebo) in acromegalic patients will be randomized. The tests will be performed under the same conditions |
Active Comparator: OGTT Tests
age and sex matched healthy volunteers
|
After inclusion, the study will include the sequential realization of 2 dynamic GH secretion tests, separated by a period of 24 hours to 30 days. Each subject will have two OGTT tests (oral administration of 75 g of glucose in 100 mL of water). The tests will be performed under the same conditions (fasting, semi-recumbent position, start of the test at 9 am) and will include a measurement of blood glucose, GH, insulinemia at -15, 0, 30, 60, 90, 120 min after ingestion of glucose or placebo. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Compare Nadir GH concentration in μg/L obtained in two OGTT in the same subject with acromegaly
Time Frame: The two test will be separated by the preiod of 24h - 30 days
|
GH will be measured by an immunometric chemiluminescent assay on an Immulite 2000XPi (Siemens Healthcare Diagnostics, Erlangen, Germany) on venous blood samples at -15, 0, 30, 60, 90, 120 min after ingestion of 75g of glucose
|
The two test will be separated by the preiod of 24h - 30 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Severity of acromegaly ("typical" form, "intermediate" form of acromegaly)
Time Frame: The two test will be separated by the preiod of 24h - 30 days
|
"Typical" form of acromegaly defined by an IGF-I concentration> 200% of the upper limit of normal, in the presence of a somatotropic pituitary adenoma • moderate or "intermediate" form of acromegaly defined by an IGF-I concentration value between 100% and 200% of the upper limit of normal, in the presence of a somatotropic pituitary adenoma. The IGF-I reference values determined by sex and age in the "Variety" study will be used for this classification |
The two test will be separated by the preiod of 24h - 30 days
|
Nadir GH in mIU / L (conversion 1 μg / L = 3 mIU / L) obtained in the two OGTT tests and the placebo (aspartame) test repeated in the same subject (acromegalic and non acromegalic)
Time Frame: Each test will be separated by the preiod of 24h - 30 days
|
Nadir GH in ug/L obtained in the two OGTT tests and the placebo (aspartame) test repeated in the same subject.
GH will be measured by an immunometric chemiluminescent assay on an Immulite 2000XPi (Siemens Healthcare Diagnostics, Erlangen, Germany) on venous blood samples at -15, 0, 30, 60, 90, 120 min after ingestion of 75g of glucose / 375g of aspartame
|
Each test will be separated by the preiod of 24h - 30 days
|
Peak glucose level in both OGTT and placebo tests
Time Frame: Each test will be separated by the preiod of 24h - 30 days
|
Verification of hyperglycemia induced or not depending on the product administered
|
Each test will be separated by the preiod of 24h - 30 days
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- P170917J
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acromegaly
-
Andrea M. IsidoriCompletedAcromegaly CardiomyopathyItaly
-
Samsung Medical CenterNot yet recruitingAcromegaly Due to Pituitary AdenomaKorea, Republic of
-
University of CopenhagenOdense University Hospital; Aarhus University Hospital; Rigshospitalet, Denmark; Aalborg University Hospital and other collaboratorsCompletedAcromegaly Due to Pituitary AdenomaDenmark
-
Immunwork, Inc.Not yet recruiting
-
Istituto Auxologico ItalianoPolitecnico di MilanoRecruiting
-
Camurus ABCompletedAcromegalyUnited States, Spain, United Kingdom, Germany, Russian Federation, Greece, Hungary, Italy, Poland, Turkey
-
CSPC ZhongQi Pharmaceutical Technology Co., Ltd.Completed
-
IpsenCompletedAcromegalyGermany, Netherlands, Sweden, Czechia, Denmark, France, Greece, Italy, Spain, United Kingdom
-
Novartis PharmaceuticalsCompletedAcromegalyItaly, Australia, Belgium, Germany, Switzerland, United States, France
Clinical Trials on Performed 3 diagnostic tests (2 OGTT tests with 75 g of Glucose and 1 placebo test with 375 mg of Aspartam
-
Liverpool Heart and Chest Hospital NHS Foundation...Completed
-
University of MichiganFood and Drug Administration (FDA)CompletedLocal Drug Concentration in Gastrointestinal TractUnited States
-
AstraZenecaCompletedHypertriglyceridemiaUnited States
-
Gilead SciencesCompletedHepatitis CUnited States, Puerto Rico
-
Tiva GroupCompletedAnesthesia Morbidity | Obesity, Morbid | Opioid Use | Post Operative Pain | Pharmacological ActionSpain
-
Memorial Sloan Kettering Cancer CenterTufts Medical Center; Lahey ClinicCompleted
-
National Cancer Institute (NCI)Active, not recruitingAdvanced Malignant Solid Neoplasm | Unresectable Malignant Solid Neoplasm | Metastatic Malignant Solid NeoplasmUnited States
-
National Cancer Institute (NCI)Eastern Cooperative Oncology Group; Cancer and Leukemia Group B; North Central...Active, not recruitingBreast AdenocarcinomaUnited States, Peru, South Africa