Initial Clinical Evaluation of an Endoscopic Therapy for Type 2 Diabetes

• Sponsor: Fractyl Laboratories, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01927562
• Collaborator: (none)
• Enrollment: 57
• Location: 1
• Arm: 1
• Actual Duration (Months): 56.1
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety and feasibility of the Fractyl Duodenal Remodeling System for the treatment of patients with poorly controlled Type 2 Diabetes.

Condition or Disease	Intervention/Treatment	Phase
Type II Diabetes	Device: Fractyl Duodenal Remodeling System	N/A

Detailed Description

The purpose of this protocol is to evaluate the initial safety profile of the Fractyl System and its effect on participants with Type 2 Diabetes. This will be determined through the monitoring of adverse events and outcome measures including Mixed Meal Tolerance Test (MMTT).

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of the Fractyl Duodenal Remodeling System for the Treatment of Type 2 Diabetes
• Actual Study Start Date: Jul 13, 2013
• Actual Primary Completion Date: Apr 7, 2017
• Actual Study Completion Date: Mar 16, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Duodenal Treatment The Duodenal Remodeling procedure utilizes both a trans-oral over the wire and endoscopic approach to minimally invasively ablating and remodeling the duodenum.	Device: Fractyl Duodenal Remodeling System

Outcome Measures

Primary Outcome Measures

1. Changed in Mixed Meal Tolerance From Baseline to 3 Months [3 months]

   Improvement in fasting plasma glucose based on Mixed Meal Tolerance Test between baseline and 3 months

Eligibility Criteria

Criteria

• Ages Eligible for Study: 28 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Participants Age > 28 years and ≤ 75 years

2. Male or Female

3. Participants with Type 2 Diabetes who are treated for ≤ 10 years and are on stable oral diabetic medications for a minimum of 3 months

4. Participants with an HbA1c > 7.5 and ≤ 10.0%

5. Participants with a BMI > 24 and < 40

6. Participants willing to comply with study requirements and able to understand and comply with informed consent

7. Participants who have signed an informed consent form

Exclusion Criteria:

1. Participants diagnosed with Type I Diabetes or with a history of ketoacidosis

2. Participants using insulin for more than 12 months

3. Participants with probable insulin production failure (defined as fasting C Peptide serum <1ng/mL)

4. Participants that have known autoimmune disease as evidenced by a positive anti glutamic acid decarboxylase (GAD) blood test

5. Participants requiring prescription anticoagulation therapy and/or dual anti-platelet therapy including aspirin who cannot discontinue their medication for 14 days before and 14 days after the procedure

6. Participants with iron deficiency anemia - either currently or in their history

7. Participants with current symptomatic hypocalcemia or vitamin D deficiency (routine calcium and/or vitamin D supplementation would not be excluded)

8. Participants with or a history of abnormalities of the GI tract preventing endoscopic access to the duodenum,

9. Participants with symptomatic gallstones or kidney stones at the time of screening

10. Participants with a history of pancreatitis

11. Participants with an active systemic infection

12. Participants with or a history of coagulopathy, upper gastro-intestinal bleeding c conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia

13. Participants with celiac disease

14. Participants with active malignancy. Those who have had remedial treatment and/or are cancer free for 5 years can be enrolled

15. Participants with known active hepatitis or active liver disease

16. Participants emotionally unstable or who exhibit psychological characteristics which, in the opinion of the Investigator, make the participant a poor candidate for clinical trial participation

17. Participants with previous GI surgery that could affect the ability to treat the duodenum such as participants who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions

18. Participants unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 2 weeks post procedure phase

19. Participants receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications

20. Participant with a known diagnosis or pre-existing symptoms of systemic lupus erythematosus, scleroderma or other autoimmune connective tissue disorder

21. Participants with active and uncontrolled gastroesophageal reflux disease (GERD) defined as grade II esophagitis or greater

22. Participants with active illicit substance abuse or alcoholism

23. Participants participating in another ongoing investigational clinical trial

24. Participants taking corticosteroids or drugs known to affect GI motility (i.e. Reglan)

25. Participants who are not potential candidates for duodenal exclusion surgery or general anesthesia

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	INDISA	Santiago		Chile

Sponsors and Collaborators

• Fractyl Laboratories, Inc.

Investigators

• Principal Investigator: Leonard R Gomez, MD, Centro Clinico De La Obesidad

Study Documents (Full-Text)

• Statistical Analysis Plan - Feb 21, 2020
• Study Protocol - Mar 10, 2016

More Information

Publications

None provided.

• Responsible Party: Fractyl Laboratories, Inc.
• ClinicalTrials.gov Identifier: NCT01927562
• Other Study ID Numbers: C-10000
• First Posted: Aug 22, 2013
• Last Update Posted: Mar 24, 2020
• Last Verified: Mar 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Pre-assignment Detail	A screening endoscopy is performed to visually examine the participant's GI tract to ensure they meet the requirements of the exclusion criteria concerning anatomical anomalies that would preclude the ability to complete the treatment. A biopsy is also taken to evaluate the baseline tissue.

Arm/Group Title	Duodenal Treatment
Arm/Group Description	Fractyl Duodenal Remodeling System
Period Title: Overall Study
STARTED	57
COMPLETED	19
NOT COMPLETED	38

Baseline Characteristics

Arm/Group Title	Duodenal Treatment
Arm/Group Description	Fractyl Duodenal Remodeling System
Overall Participants	57
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	55 96.5%
>=65 years	2 3.5%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.5 (8.3)
Sex: Female, Male (Count of Participants)
Female	21 36.8%
Male	36 63.2%
Race and Ethnicity Not Collected (Count of Participants)
Region of Enrollment (Count of Participants)
Chile	57 100%

Outcome Measures

1. Primary Outcome

Title	Changed in Mixed Meal Tolerance From Baseline to 3 Months
Description	Improvement in fasting plasma glucose based on Mixed Meal Tolerance Test between baseline and 3 months
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

The 5 subjects who did not receive an ablation were excluded from the efficacy population, yielding 52 subjects in the efficacy population (as-treated population).

Arm/Group Title	Duodenal Treatment
Arm/Group Description	Fractyl Duodenal Remodeling System
Measure Participants	52
FPG with MMTT at 3 months	145.3 (53.7)
FPG with MMTT at Baseline	180.9 (53.9)

Adverse Events

Time Frame	Adverse events were collected for each participant from the time of informed consent through end of study (up to 36 months after study procedure).
Arm/Group Title	Duodenal Treatment
Arm/Group Description	Fractyl Duodenal Remodeling System
All Cause Mortality
	Duodenal Treatment
	Affected / at Risk (%)	# Events
Total	0/57 (0%)
Serious Adverse Events
	Duodenal Treatment
	Affected / at Risk (%)	# Events
Total	3/57 (5.3%)
Gastrointestinal disorders
duodenal stenosis	3/57 (5.3%)	3
Abdominal Pain	1/57 (1.8%)	1
Vomiting	1/57 (1.8%)	1
Injury, poisoning and procedural complications
procedural complication	1/57 (1.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Hepatic Cancer	1/57 (1.8%)	1
Prostate cancer	1/57 (1.8%)	1
Skin and subcutaneous tissue disorders
skin ulcer	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Duodenal Treatment
	Affected / at Risk (%)	# Events
Total	43/57 (75.4%)
Blood and lymphatic system disorders
lymphadenopathy	1/57 (1.8%)	1
Cardiac disorders
angina pectoris	1/57 (1.8%)	1
Endocrine disorders
hypothyroidism	2/57 (3.5%)	2
Eye disorders
visual acuity reduced	3/57 (5.3%)	3
vision blurred	2/57 (3.5%)	2
retinopathy	1/57 (1.8%)	1
Gastrointestinal disorders
abdominal distension	11/57 (19.3%)	12
abdominal pain	10/57 (17.5%)	11
Diarrhoea	8/57 (14%)	8
Abdominal pain upper	7/57 (12.3%)	7
Change of bowel habit	4/57 (7%)	4
dyspepsia	4/57 (7%)	4
duodenal stenosis	3/57 (5.3%)	3
duodenitis	3/57 (5.3%)	3
constipation	2/57 (3.5%)	2
gastritis erosive	2/57 (3.5%)	2
oesophagitis	2/57 (3.5%)	2
vomiting	2/57 (3.5%)	2
abdominal discomfort	1/57 (1.8%)	1
abdominal pain lower	1/57 (1.8%)	1
dental caries	1/57 (1.8%)	1
dental discomfort	1/57 (1.8%)	1
flatulence	1/57 (1.8%)	1
gastric ulcer	1/57 (1.8%)	1
gingival oedema	1/57 (1.8%)	1
irritable bowel syndrome	1/57 (1.8%)	1
oesophageal ulcer	1/57 (1.8%)	1
regurgitation	1/57 (1.8%)	1
General disorders
Gait disturbance	1/57 (1.8%)	1
Peripheral swelling	1/57 (1.8%)	1
Pyrexia	1/57 (1.8%)	1
Hepatobiliary disorders
jaundice	1/57 (1.8%)	1
Infections and infestations
nasopharyngitis	4/57 (7%)	4
genital candidiasis	3/57 (5.3%)	3
candida infection	1/57 (1.8%)	1
gastroenteritis viral	1/57 (1.8%)	1
influenza	1/57 (1.8%)	1
rash pustular	1/57 (1.8%)	1
tooth abcess	1/57 (1.8%)	1
tooth infection	1/57 (1.8%)	1
vulvovaginitis	1/57 (1.8%)	1
Injury, poisoning and procedural complications
Tooth fracture	2/57 (3.5%)	2
contusion	1/57 (1.8%)	1
fall	1/57 (1.8%)	1
humerus fracture	1/57 (1.8%)	1
laceration	1/57 (1.8%)	1
meniscus injury	1/57 (1.8%)	1
procedural headache	1/57 (1.8%)	1
procedural hypertension	1/57 (1.8%)	1
skin injury	1/57 (1.8%)	1
Investigations
heart rate decreased	1/57 (1.8%)	1
Metabolism and nutrition disorders
polydipsia	9/57 (15.8%)	11
hypoglycaemia	3/57 (5.3%)	3
hyperglycaemia	2/57 (3.5%)	2
gout	1/57 (1.8%)	1
Musculoskeletal and connective tissue disorders
arthralgia	4/57 (7%)	4
back pain	4/57 (7%)	4
myalgia	3/57 (5.3%)	3
pain in extremity	2/57 (3.5%)	2
rotator cuff syndrome	2/57 (3.5%)	2
musculoskeletal pain	1/57 (1.8%)	1
neck pain	1/57 (1.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
acrochordon	1/57 (1.8%)	1
hepatic cancer	1/57 (1.8%)	1
prostate cancer	1/57 (1.8%)	1
Nervous system disorders
headache	2/57 (3.5%)	2
paraesthesia	2/57 (3.5%)	2
ageusia	1/57 (1.8%)	1
facial paresis	1/57 (1.8%)	1
neuropathy peripheral	1/57 (1.8%)	1
sensory loss	1/57 (1.8%)	1
Psychiatric disorders
depressed mood	3/57 (5.3%)	3
depression	3/57 (5.3%)	3
anxiety	2/57 (3.5%)	2
stress	2/57 (3.5%)	2
emotional distress	1/57 (1.8%)	1
insomnia	1/57 (1.8%)	1
panic attack	1/57 (1.8%)	1
Renal and urinary disorders
polyuria	9/57 (15.8%)	10
renal colic	2/57 (3.5%)	2
nocturia	1/57 (1.8%)	1
Respiratory, thoracic and mediastinal disorders
oropharyngeal pain	7/57 (12.3%)	7
Skin and subcutaneous tissue disorders
Acanthosis	2/57 (3.5%)	2
Rash	1/57 (1.8%)	1
Rash erythematous	1/57 (1.8%)	1
Seborrhoeic dermatitis	1/57 (1.8%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

All information received by PRINCIPAL INVESTIGATOR from SPONSOR, including, but not limited to, the Protocol, and all information developed during the Study is confidential information ("Confidential Information"), which is the sole and exclusive property of SPONSOR during the period of this Agreement and subsequent thereto.