Trial Outcomes & Findings for Renew NCP-5 for the Treatment of Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild Dementia of the Alzheimer's Type (NCT NCT03721705)

Last Updated: 2022-05-11

Results Overview

The vADAS-cog assessment includes 17 subscale scores. The total score is the sum of all scaled scored from 0-120. The higher values represent more cognitive impairment. The change in vADAS-cog scores from baseline at the timepoints of 12, 18, and 24 weeks is averaged together for each patient. The primary outcome measure is the average of those values for all patients in a group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

190 participants

Primary outcome timeframe

24 weeks

Results posted on

2022-05-11

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment Arm The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Overall Study STARTED	95	95
Overall Study COMPLETED	85	77
Overall Study NOT COMPLETED	10	18

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Arm The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Overall Study Adverse Event	2	0
Overall Study Withdrawal by Subject	4	10
Overall Study No Suitable Study Partner	1	0
Overall Study Early Termination Due to Coronavirus Disease 2019 (COVID-19)	3	7
Overall Study Death	0	1

Baseline Characteristics

Renew NCP-5 for the Treatment of Mild Cognitive Impairment Due to Alzheimer's Disease (AD) or Mild Dementia of the Alzheimer's Type

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Arm n=95 Participants The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm n=95 Participants The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Total n=190 Participants Total of all reporting groups
Age, Continuous	68.5 years STANDARD_DEVIATION 7.69 • n=5 Participants	68.1 years STANDARD_DEVIATION 7.20 • n=7 Participants	68.3 years STANDARD_DEVIATION 7.43 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants	61 Participants n=7 Participants	117 Participants n=5 Participants
Sex: Female, Male Male	39 Participants n=5 Participants	34 Participants n=7 Participants	73 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	77 Participants n=5 Participants	78 Participants n=7 Participants	155 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	13 Participants n=5 Participants	13 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) White	76 Participants n=5 Participants	78 Participants n=7 Participants	154 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	95 participants n=5 Participants	93 participants n=7 Participants	188 participants n=5 Participants
Region of Enrollment Ireland	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants
Mild Cognitive Impairment (MCI) due to AD	69 Participants n=5 Participants	68 Participants n=7 Participants	137 Participants n=5 Participants
Mild AD	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Low/Medium Cardiovascular Risk	62 Participants n=5 Participants	61 Participants n=7 Participants	123 Participants n=5 Participants
High/Very High Cardiovascular Risk	33 Participants n=5 Participants	34 Participants n=7 Participants	67 Participants n=5 Participants

PRIMARY outcome

Timeframe: 24 weeks

Population: There were 7 treatment and 11 active sham with missing VADAS-cog values at 12, 18, and 24 weeks. These 18 subjects with all 3 primary time points missing discontinued the study. These values were multiply imputed from the longitudinal model as pre-specified.

Outcome measures

Outcome measures
Measure	Treatment Arm n=95 Participants The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm n=95 Participants The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Mean Change From Baseline to 24 Weeks in Vascular Dementia Assessment Scale Cognitive Subscale (vADAS-cog) Using the Average of Scores at 12, 18 and 24 Weeks.	-9.76 score on a scale Standard Error 1.54	-5.31 score on a scale Standard Error 1.73

SECONDARY outcome

Timeframe: 24 weeks

Population: 3 participants from active sham group were migrated to treatment group.

Outcome measures

Outcome measures
Measure	Treatment Arm n=98 Participants The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm n=92 Participants The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Number of Participants With Treatment Related Adverse Events as Assessed by MedDRA.	41 Participants	33 Participants

SECONDARY outcome

Timeframe: 24 weeks

Population: 3 participants from active sham group were migrated to treatment group.

Outcome measures

Outcome measures
Measure	Treatment Arm n=98 Participants The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm n=92 Participants The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Number of Participants With Treatment Related Serious Adverse Events as Assessed by MedDRA.	8 Participants	9 Participants

Adverse Events

Treatment Arm

Serious events: 8 serious events

Other events: 41 other events

Deaths: 0 deaths

Sham Arm

Serious events: 9 serious events

Other events: 31 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Additional Information

Billy Tally, CEO

Renew Research

Phone: 949-545-8466

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Treatment Arm n=98 participants at risk The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm n=92 participants at risk The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Reproductive system and breast disorders Endometrial Cancer	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Cardiac disorders Bradycardia	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Gastrointestinal disorders Diarrhea	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
General disorders Chest Pain	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Coronavirus Infection	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Diverticulitis	1.0% 1/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Pneumonia	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Sepsis	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Urinary Tract Infection	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Cervical Vertebral Fracture	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Hip Fracture	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Amyotrophic Lateral Sclerosis	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Ataxia	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Syncope	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Transient Ischemic Attack	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Renal and urinary disorders Urinary Incontinence	1.0% 1/98 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Vascular disorders Hypotension	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.

Measure	Treatment Arm n=98 participants at risk The first four sessions will be the escalation phase using the Renew NCP-5. There will be a 5-minute ramp up period where the pressure is increased 1 psi/min until the desired pressure is reached. The goal for the treatment group will be at least 2.5 psi for the first treatment, and then escalate the pressure gradually through the fourth session with an average goal of 3 psi/session. After the fourth session, the pressure will be slowly increased to reach the maximum level the subject can tolerate with a goal of reaching 3-6 psi. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.	Sham Arm n=92 participants at risk The subjects will receive the same initial and maintenance treatment regimen on the Renew NCP-5. The pressure will not exceed an average of 0.5 psi over all treatments. Renew NCP-5: Treatment will be given 3-5 times a week for a total of 35 treatments over 12 weeks.
Injury, poisoning and procedural complications Skin Irritation/Injury	15.3% 15/98 • Number of events 20 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	3.3% 3/92 • Number of events 5 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Upper Respiratory Tract Infection	6.1% 6/98 • Number of events 7 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	7.6% 7/92 • Number of events 7 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Metabolism and nutrition disorders Dehydration/Fluid Volume Decrease	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	3.3% 3/92 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Vascular disorders Hypotension	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	4.3% 4/92 • Number of events 4 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Diverticulitis	3.1% 3/98 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Skin and subcutaneous tissue disorders Dermatitis	4.1% 4/98 • Number of events 4 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Gastrointestinal disorders Diarrhea	5.1% 5/98 • Number of events 5 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Gastrointestinal disorders Gastrointestinal Upset	6.1% 6/98 • Number of events 6 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Musculoskeletal and connective tissue disorders Joint Pain	3.1% 3/98 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Limb Fractures	3.1% 3/98 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Musculoskeletal and connective tissue disorders Back Pain	6.1% 6/98 • Number of events 8 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	1.1% 1/92 • Number of events 1 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Gastrointestinal disorders Nausea and Vomiting	3.1% 3/98 • Number of events 4 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Dizziness	3.1% 3/98 • Number of events 4 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Non-Site Specific Injury	3.1% 3/98 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 5 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Cardiac disorders Supraventricular Arrhythmias	3.1% 3/98 • Number of events 3 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
General disorders Dental pain	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Headaches	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Respiratory, thoracic and mediastinal disorders Coughing	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Skin and subcutaneous tissue disorders Skin discomfort	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Infections, other	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Muscles/Tendon/Ligament injury	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Numbness/Tingling	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Nervous system disorders Itch	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Cardiac disorders Rate and Rhythm Disorders, Other	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Site specific injuries, other	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Coronavirus Infection	2.0% 2/98 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	0.00% 0/92 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
General disorders General pain and discomfort	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Injury, poisoning and procedural complications Spinal Fractures	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 4 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Infections and infestations Urinary Tract Infection	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.
Vascular disorders Elevated Blood Pressure	0.00% 0/98 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.	2.2% 2/92 • Number of events 2 • The period from signing informed consent to the end of the study treatment follow-up (Month 12). 3 participants from active sham group were migrated to treatment group.