Pramlintide Combined With Model Predictive Control Algorithm (ALM002)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified September 2011 by University of Virginia.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
The Paul Manning Foundation (private)
Information provided by (Responsible Party):
Anthony McCall, University of Virginia
ClinicalTrials.gov Identifier:
NCT01434862
First received: September 7, 2011
Last updated: September 15, 2011
Last verified: September 2011
  Purpose

This is a scientific research study that will look at how a "closed-loop" system and the drug Pramlintide may work together to improve blood sugar control in people with type 1 diabetes mellitus. Pramlintide is approved by the Food and Drug Administration (FDA) and is given as an injection (subcutaneous) that works with insulin to lower blood sugar.


Condition Intervention
Type 1 Diabetes Mellitus
Drug: Closed loop with pramlintide
Device: Closed loop without pramlintide
Drug: Open loop with pramlintide

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pramlintide Combined With Model Predictive Control Algorithm

Resource links provided by NLM:


Further study details as provided by University of Virginia:

Primary Outcome Measures:
  • Percent of Blood glucose tests within target range of 70 to 180 mg/dl [ Time Frame: 24 hours ] [ Designated as safety issue: Yes ]

    Percent of Blood glucose tests within target range of 70 to 180 mg/dl

    The primary outcome variable of glucose control within an American Diabetes Association [ADA] standard target range between 70 mg/dl to 180 mg/dl on a Yellow Springs Instument [YSI] glucose analyzer. This is based upon the sample size estimate difference expected for % time within target range between artificial pancreas vs. patient control vs. Pramlintide plus artificial pancreas.



Secondary Outcome Measures:
  • Percent of Continuous Glucose Monitoring System [CGMS] estimated blood glucose within target range of 70 to 180 mg/dl [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
    A secondary analysis will be performed using the Continuous Glucose Monitoring [CGM] data estimated blood glucose within the American Diabetes Association [ADA] recommended target of 70-180 mg/dl.


Estimated Enrollment: 18
Study Start Date: February 2011
Estimated Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Closed loop with pramlintide
Pramlintide will be provided to study subjects who will subsequently be admitted for inpatient testing with the closed loop system. The term closed loop refers to insulin adjustment automatically regulated by computer input to the insulin pump based on monitoring (often a combination of patient blood glucose [BG] testing and/or continuous glucose monitoring [CGM]).
Drug: Closed loop with pramlintide
Dose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily.
Experimental: Closed loop without pramlintide
This visit is necessary to assess how well the closed loop system works without the pramlintide (how well it protects from hypoglycemia and hyperglycemia). It will be the exact protocol as for the closed loop with pramlintide but without the medication.
Device: Closed loop without pramlintide
This visit will assess how well the closed loop system works without the pramlintide.
Experimental: Open loop with pramlintide
The term open loop refers to insulin infusions regulated in their delivery based on patient self-monitoring and adjustment. The study subject will be in charge of their insulin treatment while also receiving pramlintide.
Drug: Open loop with pramlintide
Dose of pramlintide will be titrated based on subject's current prescribed dose. The target dose is 60 mcq three times daily.

Detailed Description:

The objective of this study is to test whether standard pramlintide treatment plus a closed-loop insulin therapy is more efficacious in controlling glycemia than either of the individual therapies. The control algorithm is in effect an insulin dose calculator for mimicry of basal insulin secretion by estimating requirements for basal rates of insulin pump infusion based on current and past glucose levels estimated from the Continuous Glucose Monitor (CGM) device and prior insulin infusions. The closed-loop system-recommended insulin will replace for 24 hours (in a clinical setting) the basal rate insulin that the patient would normally use. The patients' meal insulin needs will be estimated using an insulin-to-carbohydrate ratio as per standard clinical practice and will be optimized prior to admission to the General Clinical Research Center [GCRC].

The primary goal of this feasibility study is to test the hypothesis that the combination of a closed loop system (Open-Loop Informed with a Model Predicted Control [MPC] algorithm plus a safety system module [SSM]) with pramlintide (a synthetic analog of the hormone amylin which in health is released by the β-cells along with insulin) treatment will improve glucose control versus each of the individual therapies. Because pramlintide reduces hyperglycemia extremes generated at meals and closed loop control markedly reduces the risk of hypoglycemia, thus representing potentially important complementary actions to reduced variability — the investigators expect to find decreased hyperglycemia while simultaneously decreasing hypoglycemia risks.

Secondary goals are to explore factors associated with achieving safer and/or more effective closed loop control. For example, based upon our work in animal models, one secondary goal is to explore whether moderate inhibition of α-cell glucagon, known to occur with pramlintide administration in the early postprandial period, has the potential to repair inadequate glucagon counterregulation.

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Clinical diagnosis of type 1 diabetes for at least one year and using an insulin pump for at least six months (the diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide level and antibody determination are not needed).
  • Age 21 to 65 years
  • For females, not currently known to be pregnant
  • An understanding of the protocol and a willingness to follow it
  • HbA1c between 7 and 9%
  • Normal renal function (determined utilizing the comprehensive metabolic panel at screening with the Modification of Diet in Renal Disease [MDRD] formula and defined by estimated Glomerular Filtration Rate (eGFR) of ≥60 ml/min/1.73 m2.
  • Hematocrit >36 (females); >38 (males)

Exclusion Criteria:

  • Known hypersensitivity to SYMLIN or any of its components, including metacresol
  • Poor compliance with current insulin regimen
  • Poor compliance with prescribed self-blood glucose monitoring
  • HbA1c <7 or >9%
  • Severe hypoglycemia resulting in seizure or loss of consciousness in the 2 weeks prior to enrollment
  • Active infection
  • Current use of dietary supplements (subjects may be enrolled if they stop taking dietary supplements two weeks prior to admission and for the duration of their participation)
  • Active gastroparesis
  • Use of drugs that stimulate gastrointestinal motility (e.g. metoclopramide)
  • Diabetic ketoacidosis in the past 3 months
  • Current treatment for a seizure disorder
  • Cystic fibrosis
  • Asthma requiring hospitalization or treatment with oral steroids within the past year
  • Presence of a uncontrolled adrenal disorder
  • A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:

    • Inpatient psychiatric treatment in the past 6 months
    • Abnormal liver function (Transaminase >2 times the upper limit of normal)
    • Heart failure
    • Coronary artery disease
    • Arrhythmia
    • Seizure disorder
    • Any carcinogenic disease
    • Creatinine concentration above the upper limit of normal for age and sex
    • Active coronary artery disease
    • Uncontrolled thyroid disease
    • Use or abuse of alcohol
    • Active kidney dialysis
    • If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
    • Note: adequately treated thyroid disease and celiac disease do not exclude subjects from enrollment
  • Addison's disease
  • Current use of a beta blocker medication
  • Hematocrit < 36 (female), <38 (male)
  • Current use of oral glucocorticoids or other medications, which in the judgment of the investigator would be a contraindication to participation in the study
  • Allergy to the sensor or to one of its components
  • Continued use of acetaminophen.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01434862

Contacts
Contact: Laura Kollar, RN 434-982-6479 llk7m@virginia.edu
Contact: Molly McElwee, RN 434-982-3459 mkm6x@virginia.edu

Locations
United States, Virginia
University of Virginia, Center for Diabetes Technology Recruiting
Charlottesville, Virginia, United States, 22903
Contact: Mary Oliveri, MS, CCRP    434-982-0602    mc7m@virginia.edu   
Principal Investigator: Anthony McCall, M.D., Ph.D.         
Sub-Investigator: Stacey Anderson, MD         
Sub-Investigator: Sue Brown, M.D.         
Sub-Investigator: Susan Demartini, M.D.         
Sub-Investigator: Boris Kovatchev, Ph.D.         
Sub-Investigator: Marc Breton, Ph.D.         
Sub-Investigator: Colleen Hughes, Ph.D.         
Sponsors and Collaborators
University of Virginia
The Paul Manning Foundation (private)
Investigators
Principal Investigator: Anthony McCall, M.D., Ph.D. University of Virginia
  More Information

No publications provided

Responsible Party: Anthony McCall, Professor of Diabetes, University of Virginia
ClinicalTrials.gov Identifier: NCT01434862     History of Changes
Other Study ID Numbers: 15401
Study First Received: September 7, 2011
Last Updated: September 15, 2011
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Virginia:
Type 1 Diabetes Mellitus

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Pramlintide
Islet Amyloid Polypeptide
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Appetite Depressants
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 22, 2014