If you had $1,500,000 to spend on a clinical trial evaluating Vitamin C for any cardiovascular condition(s) of your choice, how would you design the trial?
I've set up a crude excel template (downloadable here) to help determine the costs of the trial for this brainstorming exercise. It takes into account the number of patients that would have to be screened, the number of patients that will be enrolled, the total duration of the study, length of treatment, daily dose of vitamin C used, the number of follow-up visits, the tests used, and administrative costs.
Oh, and you have to give your trial a name:
Ascorbate in the Treatment of Essential Hypertension in Non-Diabetic Patients (ATTEND)
Condition: Primary hypertension in untreated, non-diabetic patients
Intervention: 1000 mg ascorbate 3x a day = 3000 mg/day
500 mg ascorbate 3x a day = 1500 mg/day
Inclusion criteria: Men and women aged 18-55. Systolic blood pressure between 120 and 160.
Exclusion criteria: Pregnancy or lactating. Diabetes. History of cancer. History of autoimmune conditions. History of cardiovascular events e.g. stroke,myocardial infarction, PCI, CABG. Concomitant NSAID use. Any surgical procedures within the last 12 months. Secondary hypertension. Abnormal creatinine clearance rate. Proteinuria. Renal disease. Abnormal renin levels. HIV. Current or prior use of antihypertensive medications e.g. ACE inhibitors or beta-blockers. History of trauma. Use of vitamin C supplements in previous six months. Excessive alcohol intake. Hyperkalemia. Current use of psychiatric medications. Participation in clinical trial in previous six months. Concomitant use of hormonal therapies.
Rationale: Previous randomized have shown a moderate, short-term effect of vitamin C supplementation on hypertension, although data is conflicting. Epidemiological studies also show an inverse relationship between plasma ascorbate levels and blood pressure in young populations.
Design: Double-blind, randomized, placebo-controlled study
Three treatment arms (placebo, 1500 mg/day, 3000mg/day)
36 patients in placebo arm, 72 patients in each experimental group (180 patients in total)
Patients will be enrolled for 12 months, with a follow-up visit every three months
At each visit, blood pressure, plasma ascorbate levels, cholesterol, Lp(a), C-reactive protein, blood glucose, creatinine clearance rate, urine electrolytes and urine albumin will be measured. Patients will also be required to bring in their pill bottles for a pill count to record compliance, and to complete a food frequency questionnaire.
Primary end-points: Mean change in daytime ambulatory systolic blood pressure and diastolic blood pressure from baseline
Secondary end-points: Mean changes in total cholesterol, LDL:HDL ratio, Lp(a), C-reactive protein, blood glucose, plasma ascorbate levels, and creatinine clearance rate from baseline
Number of patients: 180
Estimated length of trial: 30 months
Please feel free to comment.