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Adding Liraglutide to High Dose Insulin: Breaking the Cycle

This study has been completed.
Sponsor:
Collaborator:
Novo Nordisk A/S
Information provided by (Responsible Party):
Ildiko Lingvay, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:
NCT01505673
First received: January 4, 2012
Last updated: May 3, 2017
Last verified: May 2017
January 4, 2012
May 3, 2017
January 2012
June 2016   (Final data collection date for primary outcome measure)
Glycemic control measured by HbA1c [ Time Frame: 2-months and 6-months ]
Same as current
Complete list of historical versions of study NCT01505673 on ClinicalTrials.gov Archive Site
  • Pancreatic and Hepatic triglyceride content [ Time Frame: 6-months ]
    Magnetic Resonance Spectroscopy scan of liver and pancreas
  • Weight [ Time Frame: 1-, 2-, 4-, and 6-months ]
  • Beta-Cell Function [ Time Frame: 6-months ]
    Mixed Meal Challenge Test over 4 hours measuring glucose, c-peptide, and insulin. Then C-peptide area under the curve (AUC)and change in c-peptide over change in glucose will be calculated.
  • Glucagon [ Time Frame: 6-months ]
    Measured during mixed meal challenge test.
  • Total Daily Insulin Dose [ Time Frame: 1-, 2-, 4-, and 6-months ]
    Calculated at each visit by summing all insulin shots of all types over a 24 hrs period. The average of the 3 most recent 24 hrs prior to each visit will be used.
  • Number of daily injections [ Time Frame: 1-, 2-, 4-, and 6-months ]
    Counted by adding all shots regardless of the type of insulin. The average of the 3 most recent 24 hrs prior to each visit will be used.
  • Blood Pressure [ Time Frame: 1-, 2-, 4-, and 6-months ]
  • Lipid Profile [ Time Frame: 1-, 2-, 4-, and 6-months ]
  • Liver Function blood test [ Time Frame: 1-, 2-, 4-, and 6-months ]
  • Hypoglycemic Events [ Time Frame: 3-, 7-, 14-days and 1-, 2-, 4-, and 6-months ]
    Reported by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl
  • Quality of Life Survey [ Time Frame: 6-months ]
Same as current
Not Provided
Not Provided
 
Adding Liraglutide to High Dose Insulin: Breaking the Cycle
Adding Liraglutide to High Dose Insulin: Breaking the Cycle

The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (>1.8 units/kg/day) in patients with uncontrolled (HbA1c >7.5%) type 2 diabetes mellitus will improve blood sugar control.

It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.

Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.

Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.

The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.

Interventional
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
  • Type 2 Diabetes Mellitus
  • Obesity
  • Drug: Liraglutide
    Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
    Other Name: Victoza
  • Drug: Saline
    Placebo injection of 1.8mg saline once daily for 6-months
  • Active Comparator: Liraglutide
    Intervention: Drug: Liraglutide
  • Placebo Comparator: Saline injection
    Intervention: Drug: Saline
Vanderheiden A, Harrison L, Warshauer J, Li X, Adams-Huet B, Lingvay I. Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes: A Randomized Clinical Trial. JAMA Intern Med. 2016 Jul 1;176(7):939-47. doi: 10.1001/jamainternmed.2016.1540.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
98
June 2016
June 2016   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Type 2 diabetes mellitus
  • Insulin dose of >1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)
  • HbA1c ≥ 7.5% and ≤ 11%
  • Age ≥ 18
  • Stable comorbidities on stable treatment regimens
  • Stable dose of all oral hypoglycemics for ≥ 3 months prior to enrollment
  • Ability to provide informed consent before any trial-related activities

Exclusion Criteria:

  • Type 1 diabetes mellitus
  • Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)
  • History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)
  • End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c
  • Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)
  • Unstable or decompensated comorbidities
  • Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome
  • Severe gastroparesis
  • Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures
  • Organ transplant recipient or waiting list candidate
  • Steroid use (current or potential use during the trial)
  • Known/suspected allergy to trial medication, excipients, or related products
  • Contraindications to study medications, worded specifically as stated in the product's prescribing information
  • Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT01505673
IIS-000235
Yes
Not Provided
Not Provided
Ildiko Lingvay, University of Texas Southwestern Medical Center
Ildiko Lingvay
Novo Nordisk A/S
Principal Investigator: Ildiko Lingvay, MD UT Southwestern
University of Texas Southwestern Medical Center
May 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP