TABLE 4.
Crossover Study Motor Outcomes: Intent-to-Treat Population (N = 34)
| Outcome | Varenicline LS, Mean (SE) | Placebo LS, Mean (SE) | Treatment Difference (95% CI) | p |
|---|---|---|---|---|
| Primary outcomesa | ||||
| Gait speed–normal pace–no dual task, cm/s | 121.27 (1.36) | 124.89 (1.36) | −3.62 (−5.92, −1.32) | 0.003b |
| JERK, m2/s5 | 0.97 (0.20) | 1.04 (0.20) | −0.07 (−0.44, 0.31) | 0.73 |
| Secondary outcomes | ||||
| MDS-UPDRS III | ||||
| Total | 31.90 (1.15) | 28.77 (1.13) | 3.13 (0.45, 5.80) | 0.02b |
| PIGD subscore | 4.41 (0.32) | 4.89 (0.32) | −0.48 (−1.32, 0.36) | 0.25 |
| Gait | ||||
| Gait speed–normal pace–dual task | 114.99 (1.48) | 116.26 (1.48) | −1.27 (−4.03, 1.49) | 0.35 |
| Gait speed–fast pace–no dual task | 148.92 (1.73) | 151.26 (1.73) | −2.34 (−5.71, 1.04) | 0.17 |
| Gait speed–fast pace–dual task | 135.61 (2.08) | 137.76 (2.08) | −2.14 (−5.06, 0.78) | 0.14 |
| Gait speed–normal pace–dual task minus gait speed–normal pace–no dual task | −6.07 (1.11) | −9.10 (1.11) | 3.03 (0.53, 5.54) | 0.02b |
| Normal pace dual task cost | −5.34 (0.91) | −7.59 (0.91) | 2.25 (0.28, 4.22) | 0.03b |
| Gait speed–fast pace–dual task minus gait speed–fast pace–no dual task | −13.40 (1.37) | −13.81 (1.36) | 0.41 (−2.28, 3.11) | 0.76 |
| Fast pace dual task cost | −9.28 (0.95) | −9.26 (0.95) | 0.03 (−1.76, 1.71) | 0.98 |
| Cadence–normal pace–no dual task | 109.50 (0.58) | 111.73 (0.58) | −2.23 (−3.63, −0.83) | 0.003b |
| Cadence–fast pace–no dual task | 120.70 (0.85) | 121.97 (0.85) | −1.27 (−2.83, 0.28) | 0.10 |
| Mean stride length–normal pace–no dual task | 132.58 (1.16) | 134.56 (1.16) | −1.98 (−3.69, −0.26) | 0.03b |
| Mean stride length–fast pace–no dual task | 147.96 (1.18) | 148.75 (1.18) | −0.79 (−2.99, 1.41) | 0.47 |
| %CV stride length–normal pace–no dual task | 3.87 (0.23) | 3.67 (0.23) | 0.20 (−0.27, 0.66) | 0.39 |
| %CV stride length–fast pace–no dual task | 3.55 (0.22) | 3.41 (0.22) | 0.14 (−0.41, 0.68) | 0.61 |
| Mean stride time–normal pace–no dual task | 1.10 (0.01) | 1.08 (0.01) | 0.02 (0.008, 0.04) | 0.004b |
| Mean stride time–fast pace–no dual task | 1.00 (0.01) | 0.99 (0.01) | 0.01 (−0.003, 0.02) | 0.12 |
| %CV stride time–normal pace–no dual task | 2.55 (0.58) | 3.36 (0.58) | −0.81 (−2.42, 0.80) | 0.31 |
| %CV stride time–fast pace–no dual task | 2.54 (0.15) | 2.63 (0.15) | −0.09 (−0.50, 0.32) | 0.67 |
| Double support–normal pace–no dual task | 0.37 (0.01) | 0.37 (0.01) | 0.006 (−0.005, 0.018) | 0.25 |
| Double support–fast pace–no dual task | 0.31 (0.01) | 0.31 (0.01) | 0.002 (−0.009, 0.013) | 0.70 |
| Mean sway velocity | 0.31 (0.03) | 0.26 (0.03) | 0.05 (−0.05, 0.15) | 0.30 |
| Sway RMS | 0.15 (0.01) | 0.14 (0.01) | 0.01 (−0.02, 0.04) | 0.43 |
Estimates (least squares or adjusted means and standard errors) and p values were obtained from a linear mixed model containing treatment sequence, treatment period, treatment group, and dependent-variable baseline value, with participant within treatment sequence as a random effect. Postural measures (JERK, mean sway velocity, RMS) analysis was based on a model with baseline eyes open–foam pad covariate and baseline eyes closed–foam pad covariate.
Nominal alpha = 0.025 owing to Bonferroni correction for 2 coprimary endpoints.
Statistically significant.
%CV = percent coefficient of variation; CI = confidence interval; JERK = time-based derivative of lower trunk accelerations; LS = least squares; MDS-UPDRS III = Movement Disorder Society Unified Parkinson’s Disease Rating Scale, part III; PIGD = postural instability and gait disorder; RMS = root mean square; SE = standard error.