A Euglycemic Insulin Clamp Study in Type 1 Diabetic Patients With Oral Insulin (ORAMED)
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

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 one intervention at a time in random
      order: (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.
    

Intervention name(s): ORMD-0801 capsules- 2x8mg; ORMD-0801 capsules- 3x8mg; ORMD-0801 capsules- 1x16mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Participants who receive this intervention first, then receive either ORMD-0801- 3x8mg or 1x16mg dose after a 3 day to 4 week interval. Participants receiving this drug as the second drug intervention will then receive the third intervention after a 3 day to 4 week interval. 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.; Participants who receive this intervention first, then receive either ORMD-0801- 2x8mg or 1x16mg dose after a 3 day to 4 week interval. Participants receiving this drug as the second drug intervention will then receive the third intervention after a 3 day to 4 week interval. 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.; Participants who receive this intervention first, then receive either ORMD-0801- 2x8mg or 3x8mg dose after a 3 day to 4 week interval. Participants receiving this drug as the second drug intervention will then receive the third intervention after a 3 day to 4 week interval. 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.
Other intervention name(s): Oral Insulin Capsules; Oral Insulin Capsules; Oral Insulin Capsules
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Oral Insulin