Parkinson Disease Treatment, Bromocriptine, Could Reduce Arterial Stiffness, Blood Pressure in Pediatric T1D

Article
Michal Schäfer, PhD

Michal Schäfer, PhD

Bromocriptine, an agent used in the treatment of Parkinson disease, could prove useful in reducing the incidence and burden of hypertension and arterial stiffness in younger patients with type 1 diabetes, according to results of a new National Institutes of Health (NIH)-funded study.

An analysis of data from a 34-participant study examining blood pressure and aortic stiffness with the dopamine receptor agonist in adolescents with type 1 diabetes, results of the study demonstrate use was associated with a 5-mmHg reduction in systolic and 2-mmHg reduction in diastolic blood pressure after the 4-week intervention period, with results also pointed to reduced ascending aortic pulse wave velocity and distensibility.

“We know that abnormalities in the large vessels around the heart, the aorta and its primary branches, begin to develop in early childhood in people with Type 1 diabetes,” said lead study author Michal Schäfer, PhD, a researcher and fourth-year medical student at the University of Colorado School of Medicine, in a statement. “We found that bromocriptine has the potential to slow down the development of those abnormalities and decrease the risk for cardiovascular disease in this population.”

Named the Bromocriptine Quick Release T1D study (BCQR-T1D), the placebo-controlled, random-order, double-blinded, cross-over study, was launched by investigators from the University of Colorado School of Medicine spurred by the recent approval of bromocriptine quick release formulation for people with type 2 diabetes. With this in mind, the study, which was funded by the NIH and is purported to be the first study to examine the effect of bromocriptine quick release versus placebo therapy on arterial health in a type 1 diabetes population, randomized patients with type 1 diabetes to either an 0.8 mg dose or identical placebo tablets.

Of note, previous data from the study demonstrated use of bromocriptine was not associated with significant changes in most measures of glycemic control in youth or adults with type 1 diabetes, but was associated with increased serum creatinine and lowered blood pressure in youth with type 1 diabetes.

In the current study, investigators sought to examine the effects on central and peripheral vasculature, through an analysis of measurements of endothelial function and central and peripheral arterial stiffness from baseline and following the study’s intervention period. Investigators pointed out inclusion criterion for the study called for all participants to be 12-21 years of age, have type 1 diabetes for at least 1 year, and have an HbA1c equal to or less than 12%.

The study protocol included 2 phases. During the first phase, the randomly assigned intervention was administered for 4 weeks, after which the team performed measurements of pulse wave velocity, relative area change, and distensibility from phase-contrast magnetic resonance imaging. Following a 4-week washout period, phase 2 of study followed an identical fashion with the alternate treatment. Overall, the trial enrolled 34 adolescents with a mean age of 15.9 (SD, 2.6) years, a mean HbA1c of 8.6% (SD, 1.1), a mean BMI percentile of 71.4 (SD, 26.1), and a mean disease duration of 5.8 years.

Upon analysis, results of the study demonstrated use of bromocriptine quick release formulation was associated with greater decreases in systolic (∆=−5 mmHg [95% CI, −3 to −7]; P <.001) and diastolic blood pressure (∆=−2 mmHg [95% CI, −4 to 0]; P=.039). Analysis of secondary endpoints of interest suggested use of bromocriptine quick release formulation was also associated with a greater reduction in ascending aortic pulse wave velocity (∆=−0.4 m/s; P=.018), increased relative area change (∆=−2.6%; P=0.083), and distensibility (∆=0.08%/mmHg; P=.017). Further analysis of MRI data from this cohort indicated bromocriptine quick release decreased pulse wave velocity (∆=−0.2 m/s; P=0.007) and increased distensibility (∆=0.05 %/mmHg; P=.013) in the thoraco-abdominal aorta compared to placebo.

“A stiff aorta predisposes a patient to other health issues, such as organ dysfunction or atherosclerosis and higher stress or strain on cardiac muscle,” Schäfer said. “We were able to take it a notch further and show, using more sophisticated metrics, that these central large arteries are impaired, and impairment among adolescents and young adults with type 1 diabetes may be decelerated with this drug.”

This study, “Bromocriptine Improves Central Aortic Stiffness in Adolescents With Type 1 Diabetes: Arterial Health Results From the BCQR-T1D Study,” was published in Hypertension.

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