Table 2.
Primary and secondary outcomes in the intent‐to‐treat analysis (corrected for study site differences at baseline)a
| Change from visit 2 | Active TENS versus placebo TENS | Active TENS versus no TENS | |||||
|---|---|---|---|---|---|---|---|
| Active TENS (n = 103) | Placebo TENS (n = 99) | No TENS (n = 99) | Group mean difference (95% CI) | P | Group mean difference (95% CI) | P | |
| Pain (6MWT, 0–10) | |||||||
| Visit 3 (randomized) | –1.8 (–2.3, –1.2)b | –0.8 (–1.4, –0.2)c | 0.0 (–0.5, 0.6) | –1.0 (–1.8, –0.2) | 0.008 | –1.8 (–2.6, –1.0) | <0.0001 |
| Visit 4 (all with TENS) | –2.0 (–2.8, –1.3)b | –1.9 (–2.7, –1.2)b | –1.9 (–2.6, –1.2)b | ||||
| Pain (5TSTS, 0–10) | |||||||
| Visit 3 (randomized) | –1.6 (–2.3, –1.0)b | –0.3 (–1.0, 0.3) | 0.2 (–0.4, 0.9) | –1.3 (–2.2, –0.4) | 0.002 | –1.8 (–2.8, –1.0) | <0.0001 |
| Visit 4 (all with TENS) | –1.9 (–2.6, –1.1)b | –1.4 (–2.2, –0.7)b | –1.3 (–2.1, –0.6)b | ||||
| Resting pain (0–10) | |||||||
| Visit 3 (randomized) | –1.9 (–2.5, –1.4)b | –0.7 (–1.3, –0.1)d | –0.5 (–1.1, 0.0) | –1.2 (–2.1, –0.4) | 0.0006 | –1.4 (–2.2, –0.6) | <0.0001 |
| Visit 4 (all with TENS) | –2.2 (–2.9, –1.6)b | –1.9 (–2.6, –1.2)b | –2.2 (–2.8, –1.5)b | ||||
| Fatigue (6MWT, 0–10) | |||||||
| Visit 3 (randomized) | –1.5 (–2.2, –0.8)b | –0.1 (–0.9, 0.7) | 0.4 (–0.3, 1.1) | –1.4 (–2.4, –0.4) | 0.001 | –1.9 (–2.9, –0.9) | <0.0001 |
| Visit 4 (all with TENS) | –1.3 (–2.0, –0.6)b | –0.9 (–1.7, –0.2)c | –0.9 (–1.7, –0.2)c | ||||
| Fatigue (5TSTS, 0–10) | |||||||
| Visit 3 (randomized) | –1.2 (–1.9, –0.5)b | 0.0 (–0.8, 0.7) | 0.8 (0.1, 1.5)d | –1.2 (–2.2, –0.2) | 0.011 | –2.0 (–3.0, –1.0) | <0.0001 |
| Visit 4 (all with TENS) | –1.1 (–1.9, –0.4)b | –0.8 (–1.6, –0.1)d | –0.6 (–1.4, 0.1) | ||||
| Resting fatigue (0–10) | |||||||
| Visit 3 (randomized) | –1.9 (–2.6, –1.2)b | –0.8 (–1.5, –0.04)d | –0.4 (–1.0, 0.4) | –1.2 (–2.2, –0.1) | 0.016 | –1.57 (–2.6, –0.6) | 0.0002 |
| Visit 4 (all with TENS) | –2.1 (–2.9, –1.4)b | –1.6 (–2.4, –0.8)b | –1.8 (–2.6, –1.1)b | ||||
| Disease impact (Revised FIQ, 0–10) | |||||||
| Visit 3 (randomized) | –8.5 (–12.9, –4.0)b | –3.4 (–6.5, –0.3)d | –1.39 (–4.4, 1.6) | –5.0 (–10.4, 0.3) | 0.074 | –7.1 (–12.4, –1.8) | 0.005 |
| Visit 4 (all with TENS) | –9.6 (–13.8, –5.4)b | –11.1 (–15.2, 7.0)b | –10.7 (–14.8, –6.6)b | ||||
| Pain (Revised FIQ, 0–10) | |||||||
| Visit 3 (randomized) | –1.3 (–1.8, –0.7)b | –0.4 (–0.9, 0.2) | –0.1 (–0.6, 0.4) | –0.9 (–1.7, –0.1) | 0.018 | –1.2 (–1.9, –0.4) | 0.0006 |
| Visit 4 (all with TENS) | –1.4 (–2.0, –0.8)b | –1.2 (–1.7, –0.6)b | –1.4 (–1.9, –0.8)b | ||||
| Pain (BPI interference, 0–10) | |||||||
| Visit 3 (randomized) | –0.9 (–1.4, –0.5)b | –0.3 (–0.7, 0.2) | –0.3 (–0.7, 0.2) | 0.7 (–1.3, 0.01) | 0.043 | –0.6 (–1.3, 0.0) | 0.048 |
| Visit 4 (all with TENS) | –1.1 (–1.6, –0.6)b | –0.9 (–1.4, –0.3)b | –1.2 (–1.7, –0.7)b | ||||
| Pain (BPI intensity, 0–10) | |||||||
| Visit 3 (randomized) | –0.8 (–1.1, –0.4)b | –0.3 (–0.6, 0.1) | 0.15 (–0.2, 0.5) | –0.5 (–1.0, 0.0) | 0.036 | –0.9 (–1.4, –0.4) | <0.0001 |
| Visit 4 (all with TENS) | –1.0 (–1.4, –0.6)b | –0.9 (–1.3, –0.5)b | –0.9 (–1.2, –0.5)b | ||||
| Fatigue (MAF GFI, 1–50) | |||||||
| Visit 3 (randomized) | –4.6 (–6.4, –2.8)b | –1.5 (–3.3, 0.4) | –0.3 (–2.0, 1.5) | –3.2 (–5.7, –0.6) | 0.009 | –4.4 (–6.8, –1.9) | <0.0001 |
| Visit 4 (all with TENS) | –4.0 (–6.0, –1.9)b | –4.3 (–6.4, –2.2)b | –3.2 (–5.1, 1.2)b | ||||
| Self‐efficacy (PSEQ, 0–60)e | |||||||
| Visit 3 (randomized) | 3.2 (0.8, 5.6)b | 1.5 (–0.9, 4.0) | 0.8 (–1.5, 3.1) | 1.6 (–1.8, 5.1) | 0.75 | 2.3 (–1.0, 5.7) | 0.28 |
| Visit 4 (all with TENS) | 5.3 (2.6, 8.0)b | 4.4 (1.7, 7.1)b | 4.2 (1.6, 6.8)b | ||||
| Pain catastrophizing (PCS, 0–52) | |||||||
| Visit 3 (randomized) | –3.4 (–5.3, –1.4)b | –3.1 (–5.1, –1.2)b | –1.4 (–3.3, 0.5) | –0.3 (–3.0, 2.5) | >0.99 | –2.0 (–4.7, 0.7) | 0.23 |
| Visit 4 (all with TENS) | –6.1 (–8.2, –3.9)b | –4.5 (–6.8, –2.3)b | –4.9 (–7.0, –2.8)b | ||||
| Fear of movement (TSK, 17–68) | |||||||
| Visit 3 (randomized) | –0.7 (–2.0, 0.6) | –0.3 (–1.7, 1.0) | –0.2 (–1.4, 1.1) | –0.4 (–2.3, 1.5) | >0.99 | –0.6 (–2.4, 1.3) | >0.99 |
| Visit 4 (all with TENS) | –0.3 (–1.6, 1.1) | –2.3 (–3.7, 0.9)b | –3.3 (–4.6, –2.0)b | ||||
| Mental quality of life (SF‐36 mental composite score, T score)e | |||||||
| Visit 3 (randomized) | 2.3 (0.2, 4.4)d | 1.2 (–0.9, 3.4) | –0.04 (–2.1, 2.0) | 1.1 (–1.9, 4.1) | >0.99 | 2.4 (–0.6, 5.3) | 0.17 |
| Visit 4 (all with TENS) | 2.1 (–0.2, 4.4) | 3.6 (1.3, 6.0)b | 2.8 (0.6, 5.0)c | ||||
| Physical quality of life (SF‐36 physical composite score, T score) | |||||||
| Visit 3 (randomized) | 2.4 (1.0, 3.7)b | 1.2 (–0.2, 2.5) | 1.4 (0.1, 2.6) | 1.2 (–0.7, 3.1) | 0.36 | 1.0 (–0.8, 2.8) | 0.58 |
| Visit 4 (all with TENS) | 3.5 (2.0, 5.1)b | 3.2 (1.6, 4.8)b | 4.4 (2.9, 5.9)b | ||||
| Anxiety (PROMIS, T score) | |||||||
| Visit 3 (randomized) | –1.1 (–2.6, 0.5) | –0.6 (–2.1, 1.0) | –0.7 (–2.1, 0.8) | –0.5 (–2.7, 1.7) | >0.99 | –0.4 (–2.5, 1.7) | >0.99 |
| Visit 4 (all with TENS) | –0.5 (–2.1, 1.2) | –1.6 (–3.3, 0.1) | –2.2 (–3.8, –0.6)c | ||||
| Depression (PROMIS, T score) | |||||||
| Visit 3 (randomized) | –2.8 (–4.2, –1.5)b | –0.1 (–1.5, 1.3) | 0.4 (–0.9, 1.7) | –2.7 (–4.7, –0.8) | 0.002 | –3.2 (–5.1, –1.3) | 0.0001 |
| Visit 4 (all with TENS) | –2.0 (–3.4, –0.6)c | –1.3 (–2.7, 0.1) | –1.2 (–2.6, 0.2) | ||||
| Self‐reported function (Revised FIQ, 0–30) | |||||||
| Visit 3 (randomized) | –2.7 (–4.0, –1.4)b | –1.4 (–2.7, –0.1)d | –0.6 (–1.8, 0.7) | –1.3 (–3.2, 0.5) | 0.25 | –2.1 (–3.9, –0.4) | 0.013 |
| Visit 4 (all with TENS) | –2.8 (–4.2, –1.4)b | –3.7 (–5.1, –2.3)b | –3.6 (–4.9, –2.3)b | ||||
| Self‐reported function (SF‐36, T score)e | |||||||
| Visit 3 (randomized) | 1.4 (0.1, 2.7)d | 0.5 (–0.8, 1.8) | 0.8 (–0.5, 2.0) | 0.9 (–1.0, 2.7) | 0.79 | 0.6 (–1.2, 2.4) | >0.99 |
| Visit 4 (all with TENS) | 2.9 (1.5, 4.4)b | 2.3 (0.9, 3.8)b | 3.0 (1.6, 4.4)b | ||||
| Self‐reported function/physical activity (IPAQ SF, % change in METs per week) | |||||||
| Visit 3 (randomized) | 8.1 (–22.0, 49.9) | 52.1 (9.0, 112.2)c | –14.2 (–37.5, 17.8) | 0.24 | 0.67 | ||
| Visit 4 (all with TENS) | 38.1 (–1.2, 93.0) | 46.3 (4.1, 105.5)d | 29.9 (–6.3, 80.1) | ||||
| Performance‐based function (6MWT, feet walked) | |||||||
| Visit 3 (randomized) | –1 (–55, 54) | –20 (–75, 36) | –42.1 (–95, 11) | 19 (–58, 96) | >0.99 | 42 (–34, 117) | >0.99 |
| Visit 4 (all with TENS) | 15 (–42, 71) | 16 (–41, 74) | –2 (–57, 53) | ||||
| Performance‐based function (5TSTS, sit‐to‐stand times in 10 seconds) | |||||||
| Visit 3 (randomized) | 0.6 (0.3, 1.0)b | 0.4 (0.0, 0.7)d | 0.1 (–0.3, 0.4) | 0.2 (–0.2, 0.7) | 0.96 | 0.6 (0.1, 1.0) | 0.008 |
| Visit 4 (all with TENS) | 0.6 (0.2, 1.0)b | 0.8 (0.4, 1.3)b | 0.6 (0.1, 1.0)c | ||||
| Performance‐based function (minutes per day of moderate‐to‐vigorous physical activity, % change) | |||||||
| Visit 3 (randomized) | –9.4 (–27.8, 13.5) | 2.5 (–18.6, 29.1) | –14.1 (–29.5, 4.7) | >0.99 | >0.99 | ||
| Visit 4 (all with TENS) | –6.8 (–27.2, 19.3) | –0.3 (–22.3, 27.9) | –17.0 (–33.9, 4.1) | ||||
a
Mean change (from baseline at visit 2) to visit 3 (after 4 weeks of home use of active TENS, placebo TENS, or no TENS) and visit 4 (after 4 weeks of home TENS use in all groups) with adjusted 95% confidence intervals (95% CIs). Change scores are presented for the randomized phase between visit 2 and visit 3, and for the difference from baseline at visit 4 when all subjects received active TENS. P values represent post hoc comparisons between groups. BPI = Brief Pain Inventory; MAF = Multidimensional Assessment of Fatigue; GFI = Global Fatigue Index (see Table 1 for other definitions).
b
P = <0.001.
c
P = <0.01.
d
P = <0.05.
e
Higher score represents improvement.