Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03991299 |
| Other study ID # |
181978 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
April 29, 2021 |
| Est. completion date |
February 11, 2022 |
Study information
| Verified date |
February 2023 |
| Source |
Vanderbilt University Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigators will recruit obese subjects with pre-diabetes or type 2 diabetes for the
proposed clinical study for 5 visits. After informed written consent is obtained, subjects
will be admitted to the Clinical Research Center, and will undergo upper endoscopic injection
of Botox into the duodenal wall. The investigators anticipate that injections of Botox into
the duodenal wall will result in significant weight loss and improvements in glucose
tolerance and duodenal nutrient sensitivity. Subjects will be studied over a period of 6
months. Subjects will be asked to complete 5 study visits: On the first visit, each subject
will undergo an oral glucose tolerance test. At visit 2, subjects will undergo an
esophagogastroduodenoscopy procedure for the delivery of Botox to the duodenal wall. Visits
3-5 will be made 1, 3, and 6 months later. On every study visit, body weight and body
composition will be recorded and oral glucose tolerance test will be performed. Nutrient
sensing test will be performed at visits 1 and 3.
Description:
Obese subjects (body mass index ≥ 30 kg/m2) with prediabetes or type 2 diabetes will be
recruited by solicitation flyers, advertisements, and mass emails. Subjects who do not
qualify for bariatric surgery, or subjects who are awaiting insurance approval for a
bariatric procedure at the Center of Surgical Weight Loss at Vanderbilt University Medical
Center will also be contacted via emails and telephone calls. Subjects will be directed to
contact the researcher (Drs. Abumrad and Sundaresan) directly for more information. The
recruiter will review inclusion and exclusion criteria and explain the study procedures,
duration of the study and potential risks. If the subject indicates interest, screening will
be performed to determine eligibility.
Subjects will undergo an initial screen by the study coordinator or research staff to assess
eligibility and ability to comply with the study requirements. Prior to each study visit,
subjects on oral anti-diabetic medications will be asked to discontinue these medications 4
days prior to their study visit. Diabetic subjects will be instructed to monitor their
pre-prandial blood glucose during this time and to contact the study physician if their blood
glucose levels are greater than 250 mg/dL for two consecutive readings. The study physician
may instruct the subject to initiate short-term insulin therapy or resume their oral
anti-diabetic medications; in either case the subject will be excluded from the study.
Subjects will be instructed to maintain their usual diet and physical activity levels for 1
week prior to each study visit and to arrive fasted for every visit (only water after
dinner).
6. Study Procedures
The subjects will be recruited for 5 study visits. After informed, written consent is
obtained, subjects will be admitted to the Clinical Research Center.
Study visit 1:
Day 1:
- Subjects will arrive after an overnight fast.
- They will undergo standard physical examination; anthropometric measurements (height,
weight, waist and hip circumference) perform body composition assessment via dual-energy
x-ray absorptiometry imaging will be recorded.
- Baseline glucose tolerance will be assessed by an oral glucose tolerance test.
- Subjects will be handed a visual analog scale questionnaire designed to capture their
perceived hunger and satiety sensations, food preferences, cravings, and feeding
behavior prior to intervention. The questions will be explained by the researcher and
subjects will be instructed to bring in the completed questionnaire on their second
visit.
- Subjects will be provided snacks and asked to return at 7 pm for the nutrient sensing
test to be performed the following day. The subject will be fed a standardized meal and
restricted to water after 8:00 pm.
Day 2
- Blood will be drawn for determination of fasting plasma insulin, and gut hormones
including ghrelin, Gastric inhibitory peptide, glucagon like peptide-1, pancreatic
polypeptide and Peptide YY.
- Subject will then consume a standardized 250 kcal liquid mixed meal containing 40 g
carbohydrates, 6 g fat, and 9 g protein within 10 minutes. Blood will be drawn at 15,
30, 60, and 120 minutes after consumption following which subject will be discharged.
Study visit 2 (within 2 weeks after the first visit):
- Subjects will undergo esophagogastroduodenoscopy procedure for the delivery of BOTOX to
the duodenal wall, to be performed by Dr. Patrick Yachimski at the Vanderbilt
Gastrointestinal Endoscopy Suite. The investigators have been exempted from
Investigational New Drug (IND) regulation for the proposed testing by the FDA.
- Subjects will be monitored for at least two hours and discharged with instructions for
follow-up and contact information of the physicians' team (Drs. Abumrad, Yachimski).
Study Visits 3-5 (1, 3, and 6 months after endoscopy): On every study visit, body weight,
body composition, food intake, and feeding behavior will be recorded and post-absorptive
glucose tolerance will be performed. Nutrient sensing test will be repeated at visit 3.
Oral Glucose Tolerance Test (Study visits 1 and 3-5):
- Day 0: Subjects will be fasting overnight (and restricted to water only after 8 pm).
- Day 1: Blood will be drawn for determining fasting blood glucose levels. At 8:00 am
subjects will drink a solution of 75 grams dextrose in 300 ml of water in 10 minutes.
Blood will be drawn at 15, 30, 45, 60, and 120 min post ingestion.
- The subject will be fed a standardized snack and discharged around noon.
Endoscopic delivery of BOTOX (Study Visit 2):
- Subjects will arrive fasted at the GI Suite in the main hospital at Vanderbilt
University for the procedure.
- Under the supervision of an anesthesiologist, subjects will be given combination of
intravenous medications, so they fall asleep. Dr. Yachimski will then pass the
endoscope, a long, flexible tube with light, video camera and channel for small
instruments including syringes through the esophagus and stomach, pylorus into the
junction of the 1st and 2nd parts of the duodenum. Botox (100 units dissolved in 200 μL
of sterile, preservative-free 0.9% Sodium Chloride) will be injected along the medial
(mesenteric) border, into the duodenal muscle wall.
Post endoscopy Care:
- Following completion of endoscopy procedure and emergence from anesthesia, subjects will
be monitored in the dedicated post-anesthesia care unit prior to discharge.
- Subjects will be provided written instructions regarding potential signs and symptoms of
adverse events, including fever, pain, bleeding, and muscle weakness. They will be
provided the physician call number for any questions or issues that may arise.
Nutrient sensing test (study visit 1 and 3):
- Day 1: After oral glucose tolerance test subjects return at 7:00 pm. They will be fed a
standardized meal and fasted overnight (restricted to water after 8:00 pm).
- Day 2: At 8:00 am, blood will be drawn for determination of fasting plasma insulin and
gut hormones stated above. Subject will then consume a standardized 250 kcal liquid
mixed meal containing 40 g carbohydrates, 6 g fat, and 9 g protein to be administered
over a 10-min period. Blood will be drawn 15, 30, 60, and 120 minutes later. At the end
of the study, subject will be provided a standardized meal/snack and discharged.
