Mineralocorticoid receptor antagonism of vamorolone: Evidence from LIONHEART and VISION-DMD clinical trials
Bibliographic record
Abstract
The effect of vamorolone, the first dissociative corticosteroid for Duchenne muscular dystrophy (DMD), at the mineralocorticoid receptor (MR) was investigated in the Phase 1 mechanistic LIONHEART study and using serum samples from boys with DMD in the pivotal VISION-DMD trial. In LIONHEART, 30 healthy adult males were randomized 1:1:1 to vamorolone 20 mg/kg, eplerenone 200 mg, or no treatment arms. A fludrocortisone challenge was administered between –9 h and 24 h after treatment. The LIONHEART primary outcome was urinary Na + /K + ratio; additional outcomes were pharmacokinetics, urine Na + and K + concentrations, and safety. In VISION-DMD, boys with DMD aged 4–7 years were treated with vamorolone 2 or 6 mg/kg/d for 48 weeks or with prednisone 0.75 mg/kg/d or placebo for 24 weeks followed by vamorolone 2 or 6 mg/kg/d for 20 weeks following a 4-week washout. Serum sample analysis from VISION-DMD used the SomaScan® 7 K assay. In LIONHEART, vamorolone reversed the decrease in urinary Na + /K + ratio induced by fludrocortisone, confirming vamorolone MR antagonism. The maximum MRA effect of vamorolone was observed at 4–6 h post dose and was detectable until approximately 10 h post dose. Vamorolone reversed fludrocortisone induced Na + retention with no evidence of decreased potassium excretion. Vamorolone 20 mg/kg was well tolerated, and results were consistent with known PK parameters. The VISION-DMD results showed vamorolone-specific increases in renin serum levels, as well as klotho, and calcium carrier proteins fetuin A and B, consistent with an MR antagonist effect. The available data confirm the MR antagonistic effect of vamorolone in humans.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.005 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.002 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".