Ravicti as therapy for bestrophinopathies: a double-blind crossover randomized controlled trial
Autosomal dominant best vitelliform macular dystrophy (BVMD) or autosomal recessive bestrophinopathy (ARB)
In this study the researchers are testing whether glycerol phenylbutyrate (Ravicti) will help make the bestrophin 1 protein work properly for patients where this does not, and are performing eye tests to see if they can measure that. The BETTER trial is a double-blind crossover trial, which means participants will receive both the placebo and the trial medication glycerol phenylbutyrate (Ravicti) during the trial. However, participants will not know which medication they are taking at either time point. Neither will the study doctor or assessors. Only the pharmacist dispensing the medication will know what treatment arm they have been assigned to. This is so the researchers can analyse all results and data gathered during the trial and see if there is an immediate effect of the glycerol phenylbutyrate (Ravicti). Dose: Colourless to pale yellow liquid. 1.1 gfmL of glycerol phenylbutyrate. 11.2 ml/m²/day (12.4 g/m²/day) body surface area given orally in three equally divided dosages rounded up to the nearest 0.5 ml for 7 days.
1. Participants capable of giving informed consent 2. Age 18 - 65 years old 3. Best corrected visual acuity recorded as better than hand movements at recruitment 4. Clinical and molecular diagnosis of ARB or BVMD 5. Able to speak and understand English
1. Participation in other CTIMP in the last 12 weeks 2. Pregnant or breastfeeding 3. Liver morbidity 4. Treatment for acute hyperammonaemia 5. Unable to speak and understand English 6. Urea cycle disorder 7. Known hypersensitivity to phenylbutyrate 8. Reduced phenylbutyrate absorption due to pancreatic insufficiency or intestinal malabsorption 9. Contraindicated concomitant medications: 9.1. Treatment with probenecid (which may inhibit the renal excretion of metabolites of 4PBA including phenylacetylglutamine and phenylacetate) 9.2. Treatment with drugs with a narrow therapeutic index that are substrates of CYP3A4 (4PBA weakly induces CYP3A4 in humans and so may decrease the systemic exposure to drugs that are its substrates of CYP3A4 e.g., alfentanil, quinidine, cyclosporine) 9.3. Treatment with midazolam (4PBA can decrease the systemic exposure of midazolam)