The main objective of this pilot study is to evaluate the efficacy of the Duodenal Mucosal Resurfacing procedure combined with GLP-1 administration and lifestyle intervention in subjects with insulindependent type 2 diabetes. Study success is…
ID
Source
Brief title
Condition
- Glucose metabolism disorders (incl diabetes mellitus)
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Protocol driven free of insulin at 6 months including and an HbA1c * 7.5%.
Secondary outcome
Secondary efficacy endpoints at 3 (if applicable) and 6 months to identify
improvement in cardiovascular, metabolic and hepatic parameters:
a. HbA1c
b. Change in HbA1c
c. Achieving target HbA1c of 7%
d. FPG
e. Change in FPG
f. Peak and AUC glucose in MMTT
g. Gut hormones in MMTT
h. Pancreatic hormones in MMTT
i. Metabolic profile from MMTT
j. HOMA IR
k. Insulin sensitivity
l. Beta cell function
m. Liver fat fraction
n. Cardiac function
o. ALT and AST
p. Change in AST and ALT
q. Fibrosis-4 (FIB-4) score
r. Change in FIB-4 score
s. Urine microalbumin
t. Blood pressure
u. DEXA body scan
The safety endpoint is the incidence rate of the following events at 6 months
and 12 months post-procedure:
a. All Procedure and device-related Serious Adverse Events (SAEs) and
Unanticipated Adverse Device Effects (UADEs)
b. All SAEs and UADEs
c. Number of hypo-glycemic events (blood glucose level of < 56 mg/dL (3.1
mmol/L) or requiring 3rd party assistance)
Feasibility endpoints:
a. DMR procedure time
b. Percentage of subjects adequately using and tolerating GLP-1
Background summary
It is currently unknown whether the DMR procedure can be effective in terms of
restoring euglycemia in already insulin dependent subjects with T2D. However,
it is shown that DMR increases the insulin sensitivity in T2D subjects who use
only oral glucose lowering medication. It is reasonably thinkable that in
insulin dependent T2D subjects with a preserved beta-cell function (as
indicated by a plasma C-peptide value of * 500 pmol/l), euglycemia and insulin
independence can be achieved after the DMR procedure when treatment with
insulin is replaced by Liraglutide to improve and preserve beta-cell function
after DMR and is additionally supported by lifestyle intervention. Each of
these 3 therapy modalities alone are not able to discontinue insulin therapy in
a large subgroup of subjects. A combined approach however, may very well be
beneficial.
The results of this pilot study will be used to estimate the effect size of the
DMR procedure combined with liraglutide administration and lifestyle
intervention. This effect size will then be used for a sample size calculation
for a subsequent randomized controlled trial.
It is hypothesized that a combined treatment with DMR, GLP-1 and lifestyle
intervention have an additional beneficial effect on cardiovascular, hepatic
and metabolic state compared to similar glucose regulation with insulin
treatment. The measures applied in this pilot will inform whether insulin
withdrawal combined with a single DMR procedure, initiation of liraglutide
administration and lifestyle intervention may improve metabolic, microbiome,
hepatic and cardiac states. Favorable indicators will warrant further
investigation of these effects. In a subsequent randomized controlled study,
the assessments with notable results in this pilot study will be repeated in
the different treatment arms.
Study objective
The main objective of this pilot study is to evaluate the efficacy of the
Duodenal Mucosal Resurfacing procedure combined with GLP-1 administration and
lifestyle intervention in subjects with insulindependent type 2 diabetes. Study
success is defined as insulin independence at 6 months after DMR with an HbA1c
level of * 7.5%. The second objective of this pilot study is to identify
cardiovascular, metabolic and hepatic health benefits accompanied by this
changed treatment strategy. The results of this pilot study will be used to
estimate an effect size of this combined treatment in previously insulin
dependent subjects. This effect size will be used for an adequate sample size
calculation for a subsequent randomized controlled trial.
Study design
- Single site (Academic Medical Center: AMC), open label study
- 24 cases with complete DMR procedure
- No randomization
- Screening visit to assess subject eligibility, followed by baseline visit and
DMR-procedure visit
- Endoscopic follow-up at 3 months.
- Follow-up of glucose parameters at 3, 6, 9, 12, 15, 18 and 24 months post-DMR
Intervention
Endoscopic Duodenal Mucosal Resurfacing (DMR) procedure, substitution of
insulin by a GLP-1 analogue (Liraglutide) with the additional support of
lifestyle counseling.
Study burden and risks
Risks: Possible side effects of study procedure (see E9)
Burden: 12 visits (see E2 - E6)
Meibergdreef 9
Amsterdam 1105AZ
NL
Meibergdreef 9
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. 28 -75 years of age
2. Treatment with long acting insulin * 5 years
3. On daily long acting insulin dose * 1 U/kg
4. BMI * 24 and * 40 kg/m2
5. HbA1c * 8.0% (64 mmol/mol)
6. Fasting C-peptide * 500 pmol/L (1.5 ng/ml)
7. Willing to comply with study requirements and able to understand and comply with informed consent
8. Signed informed consent form
Exclusion criteria
1. Diagnosed with Type 1 Diabetes or with a history of ketoacidosis
2. Fasting C-peptide < 500 pmol/L (1.5 ng/ml)
3. Current use of multiple daily doses insulin or insulin pump
4. Current use of a sulfonylurea derivate or meglitinide
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. Previous GI surgery that could affect the ability to treat the duodenum such as subjects who have had a Bilroth 2, Roux-en-Y gastric bypass, or other similar procedures or conditions
7. History of chronic or acute pancreatitis
8. Known active hepatitis or active liver disease
9. Symptomatic gallstones or kidney stones, acute cholecystitis or history of duodenal inflammatory diseases including Crohn*s Disease and Celiac Disease
10. History of coagulopathy, upper gastro-intestinal bleeding conditions such as ulcers, gastric varices, strictures, congenital or acquired intestinal telangiectasia
11. Use of anticoagulation therapy (such as phenprocoumon and acenocoumarol) and novel oral anticoagulants (such as rivaroxaban, apixaban, edoxaban and dabigatran) which cannot be discontinued for 7 days before and 14 days after the procedure
12. 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.
13. Unable to discontinue NSAIDs (non-steroidal anti-inflammatory drugs) during treatment through 4 weeks post procedure phase
14. Taking corticosteroids or drugs known to affect GI motility (e.g. Metoclopramide)
15. Receiving weight loss medications such as Meridia, Xenical, or over the counter weight loss medications
16. Persistent Anemia, defined as Hgb<10 g/dl
17. eGFR or MDRD <30 ml/min/1.73m^2
18. Active systemic infection
19. Active malignancy within the last 5 years
20. Not potential candidates for surgery or general anesthesia
21. Active illicit substance abuse or alcoholism
22. Participating in another ongoing clinical trial of an investigational drug or device
23. 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 |
|---|---|
| EudraCT | EUCTR2017-000349-30-NL |
| CCMO | NL60669.018.17 |