Phase 1 (0 - 24 Weeks) Objective:To study the effect of DMR on glycemic and mechanistic endpoints24 weeks post-procedure in subjects with T2D.Phase 2 (24 - 48 Weeks) Objective:To study the effect of DMR on glycemic endpoints for assessment…
ID
Source
Brief title
Condition
- Diabetic complications
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Efficacy Endpoint:
The primary efficacy endpoint is the change from baseline at 24 weeks in HbA1c,
DMR vs Sham and the absolute change at 12 weeks in MR-PDFF In patients with
baseline MR-PDFF > 5%, DMR vs Sham
Primary Safety Endpoint:
The primary safety endpoint is incidence rates of device or procedure related
SAEs, UADEs and AESIs DMR vs Sham through 24 Weeks post procedure.
Secondary outcome
1. HbA1c change from baseline to Week 24(Visit 9) by visit over time, DMR vs.
Sham
2. The relative MR-PDFF change from baseline to Week 12 in patients with
baseline MR-PDFF > 5%, DMR vs. Sham
3. Proportion of randomized-DMR-treated subjects with an HbA1c improvement from
baseline at 24 weeks (Visit 9) that maintain an HbA1c improvement at 48 weeks
4. Proportion of randomized-DMR-treated subjects with an MR-PDFF > 5% at
baseline and MR-PDFF improvement from baseline at 24 weeks (Visit 9) that
maintain an MR-PDFF improvement at 48 weeks
5. Fasting Plasma Glucose (FPG) change from baseline at 24 weeks DMR vs. Sham
6. FPG change from baseline to Week 24 by visit over time, DMR vs. Sham
7. Weight change from baseline at 24 weeks DMR vs. Sham
8. In randomized-DMR-treated subjects with an HbA1c improvement from baseline
at 24 weeks, average HbA1c improvement from baseline at 48 weeks
9. In randomized-DMR-treated subjects with an MR-PDFF > 5% at baseline and
MR-PDFF improvement from baseline at 12 weeks, average MR-PDFF improvement at
48 weeks
10. HOMA-IR change from baseline at 24 weeks DMR vs. Sham
Background summary
Type 2 is a condition that leads to high blood sugar. Good treatment is
important because too high blood sugar leads to complications such as eye
diseases, kidney disease, disease of nerve endings, myocardial infarction or
stroke. Currently most people use tablets that lower blood sugar. Despite the
use of tablets, in many people blood sugar is still too high in spite of these
tablets, which means there is a greater chance of the above-mentioned
complications occurring. A next step for these people could be that they are
going to use additional medication, or that they will use insulin for example.
In the function of the mucosa of the duodenum, changes occur with type 2
diabetes. The endoscopic Revita DMR procedure has been developed to remove this
mucous membrane by heating (ablation). After the procedure new mucous membrane
grows back. The first studies show that the DMR treatment is safe. In people
with type 2 diabetes who only took tablets, the HbA1C and fasting blood sugar
dropped and they also dropped about 3 kg. In this study all subjects received
DMR treatment and were not compared to a group that did not receive the
treatment (SHAM).
In the REVITA-2 study we want to compare the effect of the DMR treatment with a
SHAm treatment. There is a chance of 1 in 2 (50%) to get into the DMR group,
and also a 1 in 2 (50%) chance of getting into the sham group.
The patiënt and treating physician do not know which treatment the patient will
receive and will not be able to affect the draw in any way.
After 24 weeks, it will be announced in which group the patient is placed. If
it turns out that the patient has undergone the SHAM treatment, the patient can
then decide if he/she wants to crossover and receive the DMR procedure.
Study objective
Phase 1 (0 - 24 Weeks) Objective:
To study the effect of DMR on glycemic and mechanistic endpoints
24 weeks post-procedure in subjects with T2D.
Phase 2 (24 - 48 Weeks) Objective:
To study the effect of DMR on glycemic endpoints for assessment of
durability.
Study design
Randomized double-blind sham-controlled prospective multicenter clinical
investigation of subjects with type 2 diabetes sub-optimally controlled on 2
oral anti-diabetic medications.
• Up to 15 Investigational Sites in EU and global geographies
• Maximum of 50 training and up to 120 randomized subjects
• 1:1 randomized, double blind (subject and endocrinologist) trial comparing
DMR treatment to sham procedure
• 4 week oral anti-diabetic medication run-in to assess stability of blood
glucose control in conjunction with medication compliance and nutritional
counseling
• Oral diabetic medications held constant from start of run in period through
24 Week endpoint with predefined rescue algorithm for hypo and hyper glycemia
• Unblinding to occur at 24 Weeks and:
o Sham treatment arm to cross over to receive DMR treatment at 24 Weeks
with background medications held constant from 24 - 48 Weeks of
follow up
o DMR treatment arm to be managed according to current diabetes standard
of care for 24 - 48 Weeks of follow up
• Mechanism of action assessments, conducted in a subset of Study Sites,
include: ambulatory blood pressure monitoring (ABPM) in training case only,
Mixed Meal Tolerance Test (MMTT), Urine Micro Albumin, and Radiological Hepatic
Status
• Subject follow-up visits will occur at 7 and 14 Days (by phone) and 4, 12,
18, 24, 36 and 48 Weeks (in clinic), and 15, 21, 30 and 42 weeks (by phone)
post procedure*
* For cross-over patients that choose to undergo the active DMR treatment the
following visits are not applicable: 30 and 42 weeks (per phone), and 36 and 48
weeks (in clinic) post procedure
Intervention
Every patient will undergo an endoscopic treatment where the medical device is
placed into the duodenal. With the active patient, the device is activated and
the ablation is performed. With the sham patient, the medical device will not
be activated.
After 24 weeks, the sham patient can still be treated with an active endoscopic
procedure as described above.
Study burden and risks
As per protocol paragraph 1.5, there are risks related to the endoscopic
procedure in general, as well as, risks specific to the Fractyl Revita SystemTM
procedural treatment for Type 2 Diabetes.
Specific risks associated with the endoscopic procedure include (in
alphabetical order):
• abdominal tightness, cramping, pain
• diarrhea
• difficulty swallowing
• infection
• mucosal injury to GI tract
• pancreatitis
• perforation
• sore throat
• stricture
• transient bleeding
• worsening diabetic symptoms including hypoglycemia
Many of these risks and complications associated with the procedure would be
similar to those associated with other commonly performed endoscopic procedures
such as duodenal biopsies and endoscopic mucosal resection.
In addition to the risks listed above, the Fractyl Revita System may have
unique risks associated with its catheter and console used to complete the
procedure. This includes risks associated with the materials selected, its
design and construction. These risks include:
• Allergic reaction to the device materials or endoscopic labeling dye or
injectate
• Component degradation
• Control module delivers incorrect ablation time and temperature profile
• Device breakage
• Disarticulation of components from the device
• Device/Component lost in GI tract or wall
• Hole in hot fluid catheter balloon resulting in leakage of hot fluid
• Lost catheter component in the GI tract or wall
• Thermal damage to the duodenum wall or surrounding structures
• Unforeseen adverse events.
The benefit of the procedure is similar as when used commercially and could
result in improved control of the blood glucose levels and secondary risks
associated with this.
As the trial is performed under strict control and oversight by experienced
physicians, the risk of the study related additional activities is minimized.
The tests performed are standard tests.
Hartwell Avenue 17
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Lexington MA 02421
US
Listed location countries
Age
Inclusion criteria
1. 28-75 years of age
2. Diagnosed with Type 2 Diabetes and evidence of preserved insulin secretion.
Fasting insulin > 7.0 µU/ mL.
3. HbA1c of 7.5 - 10.0% (59-86 mmol/mol)
4. Body Mass Index (BMI) >= 24 and <= 40 kg/m2
5. Currently taking one or more oral glucose lowering medications, of which one
must be Metformin, with no changes in dose or medication in the previous 12
Weeks prior to study entry.
6. Able to comply with study requirements and understand and sign the informed
consent
Exclusion criteria
1. Diagnosed with Type 1 Diabetes or with a history of
ketoacidosis
2. Current use of Insulin
3. Current use of GLP-1 analogues
4. 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)
5. Known autoimmune disease, as evidenced by a positive Anti-
GAD test, including Celiac disease, or pre-existing symptoms
of systemic lupus erythematosus, scleroderma or other
autoimmune connective tissue disorder
6. Active H. pylori infection (Participants with active H. pylori may
continue with the screening process if they are treated via
medication.)
7. Previous GI surgery that could affect the ability to treat the
duodenum such as subjects who have had a Bilroth 2, Rouxen-
Y gastric bypass, or other similar procedures or conditions
8. History of chronic or acute pancreatitis
9. Known active hepatitis or active liver disease
10. Symptomatic gallstones or kidney stones, acute cholecystitis
or history of duodenal inflammatory diseases including
Crohn*s Disease and Celiac Disease
11. History of coagulopathy, upper gastro-intestinal bleeding
conditions such as ulcers, gastric varices, strictures,
congenital or acquired intestinal telangiectasia
12. Use of anticoagulation therapy (such as warfarin) which
cannot be discontinued for 7 days before and 14 days after
the procedure
13. Use of P2Y12 inhibitors (clopidogrel, pasugrel, ticagrelor)
which cannot be discontinued for 14 days before and 14 days
after the procedure. Use of aspirin is allowed.
14. Unable to discontinue NSAIDs (non-steroidal antiinflammatory
drugs) during treatment through 4 weeks post
procedure phase
15. Taking corticosteroids or drugs known to affect GI motility
(e.g. Metoclopramide)
16. Receiving weight loss medications such as Meridia, Xenical,
or over the counter weight loss medications
17. Persistent Anemia, defined as Hgb<10 g/dl
18. eGFR or MDRD <30 ml/min/1.73m^2
19. Active systemic infection
20. Active malignancy within the last 5 years
21. Not potential candidates for surgery or general anesthesia
22. Active illicit substance abuse or alcoholism
23. Participating in another ongoing clinical trial of an
investigational drug or device
24. Any other mental or physical condition which, in the opinion of
the Investigator, makes the subject a poor candidate for
clinical trial participation
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02879383 |
| CCMO | NL66981.018.18 |