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Trial record 1 of 9 for:    oramed
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A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02535715
First Posted: August 31, 2015
Last Update Posted: June 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Oramed, Ltd.
Information provided by (Responsible Party):
The University of Texas Health Science Center at San Antonio
  Purpose
ORAMED has developed an oral insulin that, in preliminary studies, has shown promise. In the present study investigators will perform a pharmacodynamic/pharmacokinetic study to evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients.

Condition Intervention Phase
Type 1 Diabetes Drug: ORMD-0801 capsules Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED)

Resource links provided by NLM:


Further study details as provided by The University of Texas Health Science Center at San Antonio:

Primary Outcome Measures:
  • Hepatic glucose production (Co-primary Outcome) [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Tritiated glucose infusion during procedures (Baseline and every 15minutes during procedures) Calculated from plasma(mg/kg-minute)

  • Peripheral Glucose Uptake (Co-primary Outcome) [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Tritiated glucose infusion during procedures (Baseline and every 15 minutes during procedures. Calculated from plasma (mg/kg-minute)


Secondary Outcome Measures:
  • Plasma insulin concentrations [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Baseline and every 15 minutes during procedures (microIU/mL)

  • Glucose infusion rate [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Variable glucose infusion rate needed to maintain euglycemia during procedures (mg/kg-minute)

  • Plasma glucose concentrations [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Measured at baseline and every 5 minutes during the procedures(mg/dL)

  • Plasma glucagon concentrations [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Measured at baseline and every 15 minutes during the procedures (pg/mL)

  • Plasma free fatty acid concentrations [ Time Frame: Participants will be followed during the procedures, until all 3 procedures are completed, an average of 1 month ]
    Measured at baseline and every 15 minutes during the procedures (micro mol/L)


Enrollment: 10
Study Start Date: January 2015
Study Completion Date: April 2017
Primary Completion Date: April 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ORAMED ORMD-0801 capsules
Two 8 mg ORAMED capsules containing insulin then Three 8mg ORAMED capsules containing insulin then One 16mg ORAMED capsules containing insulin
Drug: ORMD-0801 capsules
ORMD-0801 capsules are an oral insulin that has shown promise in preliminary studies. Investigators will evaluate this novel insulin preparation as a potential therapeutic option in diabetic patients.

Detailed Description:

Insulin therapy is an absolute requirement in type 1 diabetic patients. Multiple injections present a barrier to achieving normal/near-normal glucose control in diabetic patients (1). Therefore, there has been considerable interest in developing alternative routes of insulin administration. ORAMED has developed an oral insulin that, in preliminary studies, has shown promise. In the present study investigators will perform a pharmacodynamic/pharmacokinetic study to evaluate this novel insulin preparation as a potential therapeutic option in type 1 diabetic patients.

10 type 1 diabetic subjects will be studied.

Each subject will be studied on three occasions with an interval of 3 days to 4 weeks between each study. During each study subjects will receive: (i) two 8 mg ORAMED capsule containing insulin; (ii) three 8 mg ORAMED capsules containing insulin; (iii) one 16 mg ORAMED capsule containing insulin. If the fasting plasma glucose is >200mg/dl on the procedure day, the procedure will be rescheduled.

Prior to each study subjects will refrain from eating (except water) after 10 at night and report to the Clinical Research Center at approximately 7 in the morning. A catheter will be placed in an antecubital vein and a prime (40 microCuries x fasting plasma glucose/100) - continuous (0.4 microCuries/min) infusion of tritiated glucose will be started and continued until the end of the study. Plasma glucose will be monitored and if necessary during the 1st hour of tracer equilibration, a small amount of IV regular insulin will be administered to obtain a fasting plasma glucose of 100-130mg/dl. After a 3-hour tracer equilibration, subjects will ingest the ORAMED capsule containing insulin and a variable infusion of 20% glucose will be started to maintain the plasma glucose concentration between 100-120 mg/dl. Plasma samples for glucose, insulin, glucagon, and free fatty acid (FFA) concentrations and tritiated glucose radioactivity will be obtained every 5-15 minutes for 4 hours following the ingestion of the ORAMED capsule containing insulin.

Calculations: Following an overnight fast, steady state conditions prevail and the basal rate of glucose appearance equals the rate of glucose disappearance and is calculated as the tritiated glucose infusion rate divided by the tritiated glucose specific activity. Under postabsorptive conditions, Basal rate of glucose appearance primarily reflects hepatic glucose production (2). Following the ingestion of oral insulin, non-steady state conditions prevail and Ra and Rd are calculated using Steele's equation (3). Endogenous (primarily reflects liver) glucose production is calculated by subtracting the exogenous glucose infusion rate from the tracer-derived rate of glucose appearance. Endogenous rate of glucose disappearance reflects glucose uptake by all tissues in the body, but primarily reflects skeletal muscle (4).

Sample Size: The present study represents a pilot study to gain information about the absorption of oral insulin and its effect on hepatic and peripheral (skeletal muscle) glucose metabolism. This information will be used to determine whether the ORAMED oral insulin preparation represents a viable option to treat diabetic subjects, to gain information about the dose response effect of ORAMED insulin on glucose metabolism, and to provide quantitative data about the effect of oral insulin on hepatic and peripheral (muscle) glucose metabolism. Therefore, the investigators conservatively have set the sample size at 10.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Must be between 18 and 70 years of age
  • Must have type 1 diabetes
  • Must be in good general health by routine history and physical exam
  • A1c <10.0%
  • BMI = 18-40 kg/m2
  • On no medications known to affect glucose metabolism other than insulin
  • Hematocrit ≥ 34 vol%
  • Liver Function Tests < 3 x Upper Normal Limit
  • Plasma creatinine < 1.8 mg/dl

Exclusion Criteria:

  • Under 18 years of age and over 70 years of age
  • Does not have type 1 diabetes
  • A1c > 10.0%
  • BMI < 18 or > 40 kg.m2
  • On medications known to affect glucose metabolism other than insulin
  • Hematocrit ≤ 34 vol%
  • Liver Function Tests >3 x Upper Normal Limit
  • Plasma creatinine > 1.8 mg/dl
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02535715


Locations
United States, Texas
The University of Texas Health Science Center at San Antonio
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
The University of Texas Health Science Center at San Antonio
Oramed, Ltd.
Investigators
Principal Investigator: Ralph A DeFronzo, MD University of Texas
  More Information

Publications:
Responsible Party: The University of Texas Health Science Center at San Antonio
ClinicalTrials.gov Identifier: NCT02535715     History of Changes
Other Study ID Numbers: HSC20140476H
First Submitted: August 12, 2015
First Posted: August 31, 2015
Last Update Posted: June 16, 2017
Last Verified: May 2017

Keywords provided by The University of Texas Health Science Center at San Antonio:
Oral Insulin

Additional relevant MeSH terms:
Diabetes Mellitus, Type 1
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Insulin, Globin Zinc
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs