Safety & Effectiveness of Duodenal Mucosal Resurfacing (DMR) Using the Revita™ System in Treatment of Type 2 Diabetes

• Sponsor: Fractyl Laboratories, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03653091
• Collaborator: (none)
• Enrollment: 9
• Locations: 6
• Arms: 2
• Actual Duration (Months): 22.4
• Patients Per Site: 1.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The Revita™ System is being investigated to assess the ability to improve glycemic control in conjunction with diet and exercise in patients with Type 2 diabetes who are inadequately controlled with oral anti-diabetic medications. The purpose of this study is to demonstrate the safety and effectiveness of the Fractyl DMR Procedure using the Revita™ System compared to a sham procedure. At 24 weeks, subjects randomized to the DMR procedure be continued to be followed per protocol till 48 Weeks and the Sham treatment arm will be offered to cross over to receive the DMR treatment and will be followed per protocol for 24 weeks post treatment.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes	Device: Duodenal Mucosal Resurfacing (DMR); Device: Duodenal Mucosal Resurfacing Sham (Sham)	N/A

Detailed Description

The study is a randomized, double-blind sham-controlled prospective multi-center clinical investigation of subjects with T2D sub-optimally controlled on two oral anti-diabetic medications, one of which must be metformin, comparing the Fractyl DMR procedure using the Revita™ System to a sham procedure. All subjects will participate in a 4 week oral anti-diabetic medication run-in period before the procedure to confirm inadequate blood glucose control in conjunction with medication compliance and nutritional counseling. Subjects who meet all criteria after screening are randomized 2:1 (DMR to sham), with double blinding (subject and endocrinologist/Sponsor). The endoscopist is not blinded.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blind, Sham-Controlled, Prospective, Multi-Center Pilot Study to Evaluate the Safety and Effectiveness of Duodenal Mucosal Resurfacing Using the Revita™ System in the Treatment of Type 2 Diabetes
• Actual Study Start Date: Sep 28, 2018
• Actual Primary Completion Date: Aug 10, 2020
• Actual Study Completion Date: Aug 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Duodenal Mucosal Resurfacing (DMR) Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal mucosa in an upper endoscopic procedure in patients with type 2 diabetes.	Device: Duodenal Mucosal Resurfacing (DMR); The Fractyl DMR procedure utilizes the Revita™ Catheter to perform hydrothermal ablation of the duodenum. The catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DRM treatment are followed for 48 weeks while Sham subjects who cross over and undergo the DMR procedure at 24 weeks are followed for further 24 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.
Sham Comparator: Duodenal Mucosal Resurfacing Sham (Sham) Duodenal Mucosal Resurfacing Sham (Sham) treatment will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with type 2 diabetes.	Device: Duodenal Mucosal Resurfacing Sham (Sham); The Sham procedure consists of placing the Revita™ Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient.

Outcome Measures

Primary Outcome Measures

1. Change in Hemoglobin A1c (HbA1c) [24 weeks post procedure]

   Change in HbA1c from baseline in DMR vs Sham groups

Eligibility Criteria

Criteria

• Ages Eligible for Study: 28 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Men and non-pregnant women 28-65 years of age

2. Diagnosed with T2D for at least 3 years

3. A1C of 7.5 - 9.5% (59-80 mmol/mol)

4. BMI ≥ 28 and ≤ 40 kg/m2

5. On two to three oral OADs (metformin plus one to two additional OADs) with two (see note below) at least at half maximum labeled dose (or highest tolerated) with no changes in medication in the 12 weeks prior to the Screening Visit (Visit 1) (Refer to ADA Standard of Medical Care in Diabetes 2018, Table 8.3 for the maximum approved daily dose of non-insulin glucose lowering agents) (43). Note: For subjects on sulfonylurea (SU) glucose-lowering drugs for diabetes, the only SUs permitted in the study will be glipizide or glimepiride, and their doses below half maximum labeled dosing will not be an exclusion for study entry. Patients unwilling to reduce the dose of SU at the time of the DMR procedure as described by protocol will be excluded.

6. Agree to use an additional glucose-lowering treatment (eg, liraglutide, other OAD with the exception of glyburide) if recommended by the study investigator in case of persistent hyperglycemia.

7. Agree not to donate blood during their participation in the study

8. Able to comply with study requirements and understand and sign the Informed Consent Form

9. Women of childbearing potential (WOCBP) must be using two acceptable methods of contraception throughout the study

10. Women must not be breastfeeding

Exclusion Criteria:

1. Diagnosed with Type 1 Diabetes (T1D)

2. History of diabetic ketoacidosis or hyperosmolar nonketotic coma

3. Probable insulin production failure, defined as fasting C Peptide serum <1 ng/mL (333pmol/l)

4. Previous use of any types of insulin for >1 month (at any time, except for treatment of gestational diabetes)

5. Current use of injectable medications for diabetes (insulin, GLP-1RA)

6. Current use of glyburide, a sulfonylurea (SU) glucose-lowering drug for diabetes

7. Hypoglycemia unawareness or a history of severe hypoglycemia (more than 1 severe hypoglycemic event, as defined by need for third-party-assistance, in the last year)

8. Known autoimmune disease, including but not limited to celiac disease, or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder

9. Previous GI surgery that could limit treatment of the duodenum such as Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions

10. History of chronic or acute pancreatitis

11. History of diabetic gastroparesis

12. Known active hepatitis or active liver disease

13. Acute gastrointestinal illness in the previous 7 days

14. Known history irritable bowel syndrome, radiation enteritis or other inflammatory bowel disease, such as Crohn's disease

15. Known history of a structural or functional disorder of the esophagus that may impede passage of the device through the gastrointestinal tract or increase risk of esophageal damage during an endoscopic procedure, including Barrett's esophagus, esophagitis, dysphagia, achalasia, stricture/stenosis, esophageal varices, esophageal diverticula, esophageal perforation, or any other disorder of the esophagus

16. Known history of a structural or functional disorder of the esophagus, including any swallowing disorder, esophageal chest pain disorders, or drug refractory esophageal reflux symptoms

17. Known history of a structural or functional disorder of the stomach including gastroparesis, gastric ulcer, chronic gastritis, gastric varices, hiatal hernia (> 2 cm), cancer or any other disorder of the stomach

18. Known history of chronic symptoms suggestive of a structural or functional disorder of the stomach, including any symptoms of chronic upper abdominal pain, chronic nausea, chronic vomiting, chronic dyspepsia or symptoms suggestive of gastroparesis, including post-prandial fullness or pain, post-prandial nausea or vomiting or early satiety

19. Known history of duodenal ulcer, intestinal diverticula (diverticulitis), intestinal varices, intestinal stricture/stenosis, small bowel obstruction, or any other obstructive disorder of the GI tract

20. Currently have ongoing symptoms suggestive of intermittent small bowel obstruction, such as recurrent bouts of post-prandial abdominal pain, nausea or vomiting

21. Active H. pylori infection (Subjects with active H. pylori may continue with the screening process if they are treated with an appropriate antibiotic regimen)

22. History of coagulopathy, upper gastrointestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia

23. Current use of anticoagulation therapy (such as warfarin) which cannot be discontinued for 7 days before and 14 days after the procedure

24. Current use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor) which cannot be discontinued for 14 days before and 14 days after the procedure.

25. Unable to discontinue non-steroidal anti-inflammatory drugs (NSAIDs) during treatment through 4 weeks following the procedure. Use of low dose aspirin is allowed.

26. Current use of serotonergic medications (SSRI)

27. Use of systemic glucocorticoids (excluding topical or ophthalmic application or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit

28. Use of drugs known to affect GI motility (e.g. Metoclopramide)

29. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications

30. Untreated/inadequately treated hypothyroidism, defined as an elevated Thyroid-Stimulating Hormone (TSH) level at Screening; if on thyroid hormone replacement therapy, must be on stable dose for at least 6 weeks prior to Screening

31. Persistent Anemia, defined as Hemoglobin <10 g/dL

32. Subjects who have donated blood or received a transfusion in the prior 3 months

33. Subjects with conditions that alter red blood cell turnover

34. Subjects with prosthetic joints

35. Significant cardiovascular disease including known history of valvular disease, or myocardial infarction, heart failure, transient ischemic attack or stroke within the last 6 months

36. Moderate or severe chronic kidney disease (CKD), with estimated glomerular filtration rate (eGFR) <45 ml/min/1.73m2 (estimated by MDRD)

37. Known immunocompromised status, including but not limited to individuals who have undergone organ transplantation, chemotherapy or radiotherapy within the past 12 months, who have clinically-significant leukopenia, who are positive for the human immunodeficiency virus (HIV) or whose immune status makes the subject a poor candidate for clinical trial participation in the opinion of the Investigator

38. Active systemic infection

39. Active malignancy within the last 5 years (with the exception of treated basal cell or treated squamous cell carcinoma)

40. Subjects with a personal or family history of medullary thyroid carcinoma

41. Subjects with Multiple Endocrine Neoplasia syndrome type 2

42. Not a candidate for surgery or general anesthesia

43. Active illicit substance abuse or alcoholism

44. Current smoker

45. Participating in another ongoing clinical trial of an investigational drug or device

46. Any other mental or physical condition which, in the opinion of the Investigator, makes the subject a poor candidate for clinical trial participation

47. Unwilling or unable to perform SMBG, complete the patient diary, or comply with study visits and other study procedures as required per protocol

Additional exclusion criteria to be confirmed during the screening process:

1. A1c post Run-In Phase < 7.5% (59 mmol/mol) or > 9.5% (86 mmol/mol)

2. Any severe hypoglycemic event, defined as hypoglycemia requiring third-party assistance; or any clinically significant hypoglycemic event, defined as self-monitored or laboratory plasma glucose level < 54 mg/dL (3.0 mmol/L); or ≥ 2 glucose alert values ≤70 mg/dL (3.9 mmol/L), unless a clear correctable precipitating factor can be identified, since the screening visit (Visit 1)

3. Uncontrolled hyperglycemia with a glucose level >270 mg/dl (>15 mmol/L) after an overnight fast or >360 mg/dl (>20 mmol/l) in a randomly performed measurement during Medication Run-In Period and confirmed by a second measurement (not on the same day)

4. Mean of 3 separate blood pressure measurements >180 mmHg (systolic) or >100 mmHg (diastolic)

5. WOCBP with a positive urine pregnancy test at Baseline Visit

6. Active and uncontrolled GERD defined as grade III esophagitis or greater

7. Abnormalities of the GI tract preventing endoscopic access to the duodenum

8. Anatomic abnormalities in the duodenum that would preclude the completion of the DMR procedure, including tortuous anatomy

9. Malignancy newly diagnosed by endoscopy

10. Upper gastrointestinal conditions such as ulcers, polyps, varices, strictures, congenital or acquired intestinal telangiectasia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Hospital / TRANSLATIONAL RESEARCH INSTITUTE FOR METABOLISM AND DIABETES (TRI)	Orlando	Florida	United States	32804
2	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115
3	Dartmouth Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
4	University of Pennsylvania - Penn Metabolic Medicine	Philadelphia	Pennsylvania	United States	19104
5	UTHealth	Houston	Texas	United States	77030
6	Texas Diabetes Institute	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Fractyl Laboratories, Inc.

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Jul 9, 2020
• Statistical Analysis Plan - May 19, 2020

More Information

Publications

None provided.

• Responsible Party: Fractyl Laboratories, Inc.
• ClinicalTrials.gov Identifier: NCT03653091
• Other Study ID Numbers: C-40000
• First Posted: Aug 31, 2018
• Last Update Posted: Jul 26, 2022
• Last Verified: Jun 1, 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Fractyl Laboratories, Inc.: Type 2 diabetes; Diabetes Mellitus; Noninsulin-Dependent Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Revita System; Anti-diabetic medications; Duodenal Mucosal Resurfacing
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Pre-assignment Detail	All eligible subjects participated in a 4-week oral antidiabetic drug (OAD) run-in period before randomization to the index procedure to assess stability of blood glucose control in conjunction with medication compliance and lifestyle (diet, exercise) counseling. All subjects were managed according to the current diabetes standard of care.

Arm/Group Title	Duodenal Mucosal Resurfacing Procedure (DMR)	Sham Procedure (Sham)
Arm/Group Description	Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal mucosa in an upper endoscopic procedure in patients with type 2 diabetes. The Fractyl DMR procedure utilizes the Revita™ Catheter to perform hydrothermal ablation of the duodenum. The catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DRM treatment are followed for 48 weeks.	Sham treatment (Sham) will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with type 2 diabetes. The Sham procedure consists of placing the Revita™ Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient. Sham subjects who cross over and undergo the DMR procedure at 24 weeks are followed for further 24 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.
Period Title: First 24 Weeks
STARTED	6	3
Intent-to-Treat	6	3
As-Treated	5	4
Safety	5	4
COMPLETED	6	3
NOT COMPLETED	0	0
Period Title: First 24 Weeks
STARTED	5	4
Crossed Over to DMR at Week 24	0	3
COMPLETED	5	3
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Duodenal Mucosal Resurfacing Procedure (DMR)	Sham Procedure (Sham)	Total
Arm/Group Description	Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal mucosa in an upper endoscopic procedure in patients with type 2 diabetes. The Fractyl DMR procedure utilizes the Revita™ Catheter to perform hydrothermal ablation of the duodenum. The catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DRM treatment are followed for 48 weeks while Sham subjects who cross over and undergo the DMR procedure at 24 weeks are followed for further 24 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.	Sham treatment (Sham) will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with type 2 diabetes. The Sham procedure consists of placing the Revita™ Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient.	Total of all reporting groups
Overall Participants	5	4	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	5 100%	4 100%	9 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Standard Deviation) ]
Median (Standard Deviation) [years]	57.0 (3.83)	53.5 (4.20)	56.0 (3.93)
Sex: Female, Male (Count of Participants)
Female	1 20%	0 0%	1 11.1%
Male	4 80%	4 100%	8 88.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	1 25%	1 11.1%
Not Hispanic or Latino	5 100%	3 75%	8 88.9%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 20%	0 0%	1 11.1%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	2 50%	2 22.2%
White	4 80%	2 50%	6 66.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	5 100%	4 100%	9 100%
Height (cm) (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	171.44 (9.871)	176.03 (5.954)	173.48 (8.237)
Weight (kg) (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	92.24 (7.513)	94.4 (7.366)	93.2 (7.062)
Body mass index (kg/m^2) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.50 (2.630)	30.28 (1.841)	30.96 (2.268)
HbA1c (%) (mmol/mol) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/mol]	8.3 (.738)	8.73 (.512)	8.49 (.649)
Duration of T2D Diagnosis (days) (Days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Days]	4222.6 (1442)	4933 (1703.53)	4538.3 (1506.03)

Outcome Measures

1. Primary Outcome

Title	Change in Hemoglobin A1c (HbA1c)
Description	Change in HbA1c from baseline in DMR vs Sham groups
Time Frame	24 weeks post procedure

Outcome Measure Data

Analysis Population Description

The AT population is a subset of ITT subjects who received at least 1 ablation or underwent the randomized sham procedure.

Arm/Group Title	Duodenal Mucosal Resurfacing (DMR)	Duodenal Mucosal Resurfacing Sham (Sham)
Arm/Group Description	Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal mucosa in an upper endoscopic procedure in patients with type 2 diabetes. Duodenal Mucosal Resurfacing (DMR): The Fractyl DMR procedure utilizes the Revita™ Catheter to perform hydrothermal ablation of the duodenum. The catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DRM treatment are followed for 48 weeks while Sham subjects who cross over and undergo the DMR procedure at 24 weeks are followed for further 24 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.	Duodenal Mucosal Resurfacing Sham (Sham) treatment will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with type 2 diabetes. Duodenal Mucosal Resurfacing Sham (Sham): The Sham procedure consists of placing the Revita™ Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient.
Measure Participants	5	4
Mean (Standard Deviation) [mmol/mol]	-0.33 (.252)	-0.70 (.469)

Adverse Events

Time Frame	Adverse events were followed for up to a maximum of 56 weeks.
Adverse Event Reporting Description	Deaths and/or Adverse Events are reported using the Safety Population.
Arm/Group Title	Duodenal Mucosal Resurfacing Procedure (DMR)		Sham Procedure (Sham)		Sham Crossover
Arm/Group Description	Duodenal Mucosal Resurfacing (DMR) treatment will include hydrothermal ablation of the duodenal mucosa in an upper endoscopic procedure in patients with type 2 diabetes. The Fractyl DMR procedure utilizes the Revita™ Catheter to perform hydrothermal ablation of the duodenum. The catheter is delivered trans-orally over a guide-wire to first inject saline to lift the sub-mucosal space, followed by an ablation of the duodenal mucosa. Subjects who receive the DRM treatment are followed for 48 weeks while Sham subjects who cross over and undergo the DMR procedure at 24 weeks are followed for further 24 weeks post treatment. Sham subjects who choose not to cross over are discontinued from the study.		Sham treatment (Sham) will include an upper endoscopic procedure similar to DMR treatment without hydrothermal ablation of the duodenal mucosa in patients with type 2 diabetes. The Sham procedure consists of placing the Revita™ Catheter as described above into the duodenum for a minimum of 30 minutes and then removing it from the patient.		Subjects that were in sham arm until 24 weeks and then crossover to receive DMR treatment at 24 weeks and followed up for additional 24 weeks. AEs captured from time of DMR procedure through follow up to end of study.
All Cause Mortality
	Duodenal Mucosal Resurfacing Procedure (DMR)		Sham Procedure (Sham)		Sham Crossover
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/4 (0%)		0/3 (0%)
Serious Adverse Events
	Duodenal Mucosal Resurfacing Procedure (DMR)		Sham Procedure (Sham)		Sham Crossover
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/5 (0%)		0/4 (0%)		0/3 (0%)
Other (Not Including Serious) Adverse Events
	Duodenal Mucosal Resurfacing Procedure (DMR)		Sham Procedure (Sham)		Sham Crossover
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/5 (80%)		4/4 (100%)		3/3 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	0/5 (0%)		1/4 (25%)		0/3 (0%)
Ear and labyrinth disorders
Ear Pain	0/5 (0%)		1/4 (25%)		0/3 (0%)
Gastrointestinal disorders
Diarrhoea	3/5 (60%)		3/4 (75%)		2/3 (66.7%)
Abdominal Distension	0/5 (0%)		1/4 (25%)		1/3 (33.3%)
Abdominal Pain	1/5 (20%)		1/4 (25%)		0/3 (0%)
Abdominal Pain Upper	1/5 (20%)		0/4 (0%)		0/3 (0%)
Nausea	0/5 (0%)		0/4 (0%)		1/3 (33.3%)
Vomiting	1/5 (20%)		0/4 (0%)		0/3 (0%)
Abdominal Discomfort	0/5 (0%)		1/4 (25%)		0/3 (0%)
Abdominal Pain Lower	0/5 (0%)		1/4 (25%)		0/3 (0%)
Gastritis	0/5 (0%)		1/4 (25%)		0/3 (0%)
General disorders
Pyrexia	1/5 (20%)		0/4 (0%)		0/3 (0%)
Nodule	0/5 (0%)		1/4 (25%)		0/3 (0%)
Infections and infestations
Nasopharyngitis	1/5 (20%)		0/4 (0%)		0/3 (0%)
Investigations
Blood Glucose Increased	0/5 (0%)		1/4 (25%)		0/3 (0%)
Musculoskeletal and connective tissue disorders
Neck Pain	0/5 (0%)		1/4 (25%)		0/3 (0%)
Nervous system disorders
Headache	1/5 (20%)		0/4 (0%)		0/3 (0%)
Paraesthesia	1/5 (20%)		0/4 (0%)		0/3 (0%)
Presyncope	0/5 (0%)		1/4 (25%)		0/3 (0%)
Psychiatric disorders
Mental Status Changes	1/5 (20%)		0/4 (0%)		0/3 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain	2/5 (40%)		1/4 (25%)		0/3 (0%)
Respiratory Symptom	1/5 (20%)		0/4 (0%)		0/3 (0%)

Limitations/Caveats

Limitations of this pilot study include the small sample size and missing data due to COVID-19.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.