Brief episodes of limited oxygen reduction, or acute intermittent hypoxia (AIH), have been shown to enhance muscle strength in persons with spinal cord injury. Our aim is to evaluate safety of AIH for stroke survivors using intra-subject dose escalation, with dose levels of 21% (normal air), 17%, 13%, and 9% O2 content.
Sample size was determined using simulation. The null hypothesis assumed uncorrelated and low adverse event (AE) probabilities at each dose level k (p¬k=0.01). Alternative hypotheses considered several dose-toxicity curves, with AE probabilities at the first dose ranging from p1 = 0.05 to 0.125, and increasing by 0.025 or 0.05 for the second and third doses. Under the alternative hypothesis, patients’ AE occurrences were simulated as binary data, assuming within-subject correlation of 0.3. For each scenario, 10,000 trials were simulated using the bindata package in R.
AIH was declared unsafe if ?2 AE’s occurred at any dose level. Under the null, probability of declaring AIH unsafe was 0.048 when n=12 and 0.062 when n=14. Power was >80% under all dose-toxicity scenarios when p1?0.10 for n=12, and p1?0.08 for n=14.