Effect of Hyperglycemia on Gastric Emptying Interactions With Pramlintide

This is an interventional diagnostic trial for Type 1 Diabetes focused on measuring pramlintide, gastric emptying, T1DM, postprandial Read More

Inclusion Criteria:

All of the following criteria are to be fulfilled for inclusion of an individual in the study unless the investigator grants an exception:

• Clinical diagnosis of type 1 diabetes (otherwise healthy) with an HbA1 ≤ 9%, and on a stable insulin treatment for at least 3 months (preferably on pump regimen) prior to screening OR is a healthy individual.
• 20-40 years of age, inclusive.
• Understand and sign an informed consent document, communicate with the investigator, and understand and comply with the requirements of the study.
• Euthyroid, including subjects receiving thyroid replacement therapy.

If female:

• Is surgically sterilized by hysterectomy; OR
• Is post-menopausal, as documented by a history of amenorrhea for 6 months and follicle stimulating hormone (FSH) level within the range specified as post-menopausal by the reporting laboratory at screen (post menopausal women on estrogen may enter the study without obtaining an FSH level); OR
• If of childbearing potential, meets the following criteria:

negative pregnancy test (ß-HCG), regardless of birth control method (including subjects with tubal ligation);

• Practicing and willing to continue throughout the study the appropriate contraception (defined as oral, injected, or implanted contraceptives for at least 3 months prior to entry, or barrier contraception).
• Agree to take every precaution to ensure that pregnancy will not occur during the study.

Exclusion Criteria:

• Individuals meeting any of the following criteria are to be excluded from the study unless the investigator grants an exception:
• History of severe hypoglycemia.
• Body mass index (BMI) ≥ 30 kg/m2.
• Autonomic nerve dysfunction: abnormal result in the cardiovascular parasympathetic and/or sympathetic tests (screening visit).

Hepatic disease:

• Known hepatic disease or transaminases (GOT, GPT) ≥ 2x above normal values.

Renal disease:

• Known or serum urea, serum creatinine ≥ 1.5x above normal values
• Cardiovascular or pulmonary disease:
• Arterial hypertension
• Blood pressure >150/95 mmHg at screening in a sitting position)
• Arterial occlusive disease
• Known coronary heart disease
• Abnormal ECG at screening visit.
• Gastrointestinal disease:
• Any known structural gastrointestinal disorder,
• Gastrointestinal surgery except for appendectomy,
• Symptoms indicating functional or structural upper gastrointestinal disorder (pain, bloating, postprandial fullness, nausea, emesis,
• Gastroectomy, gastroparesis, lactose intolerance, and diseases known to alter small bowel absorption; e.g., inflammatory bowel disease.

CNS disease:

• Epilepsy (including subjects with a past history of convulsions associated with hypoglycaemia),
• Psychiatric illness (including history of eating disorder such as bulimia or anorexia).
• Autoimmune disease other than thyroid, pernicious anemia, or vitiligo.
• Malignant disease requiring chemotherapy,
• Any acute febrile illness within 2 weeks of Screening (Visit 1) with a temperature of 100°F,
• Currently abusing alcohol or drugs, or have a history of alcohol or drug abuse that in the investigator's opinion could cause the subject to be non-compliant; or have a general history of non-compliance with medications.
• Receipt of any investigational drug within 90 days of Screening (Visit 1) (prior treatment with pramlintide is permissible).

• Currently treated with medications known to interfere with gastric emptying such as, but not limited to:

  • Ca2+ channel antagonists, ß-receptor antagonists, prokinetic agents metoclopramide (Reglan®) and cisapride (Propulsid®); and
  • Chronic (more than 10 days within a 6-month period) macrolide antibiotics such as erythromycin and newer derivatives.

• Currently treated with:

  • Bile acid sequestering resins cholestyramine (Questran®) and colestipol (Colestid®),
  • Systemic steroids,
  • Anti-obesity agents (including orlistat [Xenical®] and sibutramine [Meridia®]),
  • Alpha-glucosidase inhibitors (acarbose [Precose®] and miglitol [Glyset®]) and meglitinides ([Prandin®] and [Starlix®]).