Brief Title
Reproducibility and Utility of OGTT in Acromegaly
Official Title
Reproducibility and Utility of Growth Hormone Inhibition by Oral Glucose Tolerance Test for the Diagnosis of Acromegaly
Brief Summary
Prospective study of reproducibility and utility of growth hormone inhibition by oral glucose
tolerance test for the diagnosis of acromegaly, in acromegalic and non-acromegalic subjects,
with a randomized double-blind crossover over placebo arm in the group of acromegalic
patients
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:
1. 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.
2. 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).
3. Evaluate OGTT-stimulated insulin secretion in acromegalic and non-acromegalic subjects.
Study Type
Interventional
Primary Outcome
Compare Nadir GH concentration in μg/L obtained in two OGTT in the same subject with acromegaly
Secondary Outcome
Severity of acromegaly ("typical" form, "intermediate" form of acromegaly) Condition
Acromegaly
Intervention
Performed 3 diagnostic tests (2 OGTT tests with 75 g of Glucose and 1 placebo test with 375 mg of Aspartam
Study Arms / Comparison Groups
OGTT Tests and Placebo Test
Description: Patients with acromegaly
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
Other
Estimated Enrollment
110
Start Date
September 10, 2019
Completion Date
December 10, 2022
Primary Completion Date
December 10, 2022
Eligibility Criteria
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.
Gender
All
Ages
18 Years - 85 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
, 01 45 21 33 98, [email protected]
Location Countries
France
Location Countries
France
Administrative Informations
NCT ID
NCT04066569
Organization ID
P170917J
Responsible Party
Sponsor
Study Sponsor
Assistance Publique - Hôpitaux de Paris
Study Sponsor
, ,
Verification Date
August 2019