Table 2 The clinical studies of SAM efficacy on knee osteoarthritis symptoms

Study design

Clinical study

Randomized, placebo-controlled clinical study

Double-blind randomized placebo-controlled clinical study

Multi-site clinical efficacy study

Demographics

Study 1: sample size (n = 12, no placebo), VAS pain focused

Study 2: sample size (n = 7, 4 active, 3 placebo), Pain and mobility focused

Sample size (n = 47, active (n = 28), placebo (n = 19)

Sample size (n = 90, 23 males, 28 females), active (n = 55), placebo (n = 35, 16 males, 17 females)

Total sample size (n = 32, 18-males, 14- females), Rapid responders (n = 24)

Clinical criteria

Knee osteoarthritis

Inclusion criteria:

Diagnosed with mild to moderate knee OA, between 35–80 years, reported a frequent pain score of 3 to 7 on the VAS during the week preceding enrollment, deemed appropriate to participate by the study physician

Exclusion criteria:

Not defined

Knee osteoarthritis

Inclusion criteria: Radiographic mild to moderate clinical knee osteoarthritis (Grade 1–2 on the OARSI scale) in one or both knees, average pain score > 4 on a 10 point (0-100 mm) VAS scale during the week prior to enrollment

Exclusion criteria:

Not defined

Knee osteoarthritis

Inclusion criteria: Age (35–80 years), mild, moderate OA K/L grade I/II, OA in one or both knees, Osteophytes, joint space, NRS between 3 and 7, self-apply device

Exclusion criteria: Severe OA (K/L III), knee replacement (TKA), surgical intervention, hyaluronic acid injection in the last 6 months, non-ambulatory patient, no corticosteroids, osteoarthritis due to secondary metabolic disorder

Knee osteoarthritis

Inclusion criteria: Age 45–85, K/L II – III grade, NRS between 3 and 7 (0–10 scale)

Exclusion criteria: Patients with no intra-articular injection in the last 6 months, no trauma, no implants or surgeries at the arthritic knee, K/L greater than III, steroid base medication, OA due to other metabolic disorders

Rapid responders: Patients reporting 1-point NRS pain reduction after the first treatment (n = 24)

Methodology

SAM therapy for 4–8 h daily

VAS: 12 – 60 days, daily pain diary was maintained by patients at home

Mobility: 6 weeks, data recorded at 2 weeks increments using actigraph. Patients also recorded pain in the morning, afternoon, and evening

SAM therapy for 4 h per day at least four times per week for six (6) weeks, recording their pain before and after treatment in dairy. Participants attended bi-weekly visits to the clinical study site to assess compliance

SAM therapy over 6 weeks, self-administered in the home setting for 4 h per day

Patients recorded NRS post-treatment, and WOMAC score was recorded after 6 weeks

Range of motion and strength testing using manual muscle tester at approximately 90 degrees

SAM therapy

NRS was recorded by patients daily pre-and post-treatment by the patient for 7 days

WOMAC score was recorded and start and end of study at the outpatient center

Outcomes

VAS: (0–100 mm)

Mobility: actigraphy

VAS: (0–100 mm)

NRS (0–10 Scale)

WOMAC (0–960, pain, stiffness, functionality)

Range of motion and strength (n = 17 sub cohort)

NRS: (0–10 pain scale)

WOMAC (0–960, pain, stiffness, functionality)

Main findings

VAS pain decreased by 52% over 60 days (p < 0.05)

20% improvement in mobility over 6 weeks

VAS pain decrease by 2.5 points (1.23 over placebo, p < 0.03) for subjects with moderate to severe starting pain

1.96 point NRS pain relative to 0.85 placebo decrease in 6 weeks (p < 0.001)

WOMAC: 505 points decrease in the active group relative to 311 points in the placebo group (p = 0.02)

In pilot subset rotational strength increased from baseline to 6 weeks (3.2 N, p = 0.03); however, no other measures were significant

2.06 point NRS pain decrease (50%, p < 0.001) was reported in the entire study cohort with a 2.96 NRS point decrease in rapid responders (70%. p < 0.001) relative to baseline NRS pain score

WOMAC scored increased by 351 in the complete cohort (p < 0.001) and 510 in rapid responders (p < 0.001)

95% of patients reported ease of use and continuation of treatment

Level of evidence

1C

1C

1B

2A

Downs and black score

17/28, fair quality

12/28, poor quality

27/28, excellent quality

23/28, good quality

Conclusion

Pain reduction in the subset of patients with no significant change in mobility. Require larger clinical study to measure mobility improvement

SAM treatment provided clinically effective pain reduction according to the Initiative on Methods, Measurements, and Pain Assessment in Clinical Trials (IMMPACT)

SAM treatment significantly decreased pain, increased mobility and rotational strength in mild to moderate OA. Further studies are required to establish effect on joint range of motion

In the efficacy study, SAM with diclofenac ultrasound gel patch showed significant effectiveness in knee OA pain alleviation and increased functionality with high usability and safety