Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03761290 |
| Other study ID # |
Shoemaker R03 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
June 19, 2019 |
| Est. completion date |
April 30, 2021 |
Study information
| Verified date |
May 2021 |
| Source |
Vanderbilt University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial Summary
It is increasingly recognized that Pseudohypoparathyroidism type 1A (PHP1A) is associated
with an increased risk of type 2 diabetes but the mechanism is unknown. In this pilot study
we will assess β-cell function in patients with PHP1A and pseudopseudohypoparathyroidism
PPHP.
Description:
Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by impaired
stimulatory G-protein signaling due to heterozygous mutations in the gene, GNAS. The most
severe form of the disease, PHP1A occurs when a GNAS mutation is inherited on the
preferentially expressed maternal allele. A less severe form of the disease,
pseudopseudohypoparathyroidism (PPHP), occurs when a GNAS mutation is inherited on the
paternal allele. Clinically, PHP1A is characterized by multi-hormone resistance, cognitive
impairment and early-onset obesity while PPHP has a mild phenotype without multi-hormone
resistance. It is increasingly recognized that PHP1A is associated with an increased risk of
type 2 diabetes but the mechanism is unknown. Glucose homeostasis and diabetes risk has not
been studied in PPHP. As part of the parent K23 award, we investigated glucose tolerance in
children with PHP1A. In contrast to the adult literature, we found that children with PHP1A
had greater insulin sensitivity than matched controls. When challenged with an oral glucose
load, however, children with PHP1A had persistent hyperglycemia and 25% met criteria for
impaired glucose tolerance. The goal of this proposal is to quantify β-cell function in
PHP1A. It is plausible that these individuals have a) impaired β-cell function, b)
differences in insulin sensitivity, and c) impaired incretin function. Thus, in this pilot
study we will definitively assess one of these, β-cell function, using the frequently sampled
intravenous glucose tolerance test in patients with PHP1A and PPHP (aim 1). We will also
assess oral glucose tolerance over time by bringing back children and young adults with PHP1A
from our original cohort for repeat glucose tolerance testing (aim 2). The ultimate goal is
to rigorously define glucose homeostasis defects in PHP1A in order to design and conduct an
intervention study for glucose intolerance and type 2 diabetes in PHP1A.
