In a subsequent randomized double-blind placebo-controlled phase II clinical trial, the antihypertensive effect of three or four subcutaneous immunizations with PMD3117 vaccine (100 μg of Ang I-KLH adsorbed on an aluminum hydroxide adjuvant) was evaluated in patients with essential hypertension; it was found that immunization with PMD3117 increased plasma renin and decreased urinary aldosterone, suggesting blockade of the RAS, but failed to decrease blood pressure [40]. This evidence concerns the gene REN and hypertensive disorder.