Adding Liraglutide to High Dose Insulin: Breaking the Cycle
15 dicembre 2017 aggiornato da: Ildiko Lingvay
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.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
71
Fase
- Fase 4
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
-
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Texas
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Dallas, Texas, Stati Uniti, 75390
- UT Southwestern
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-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
18 anni e precedenti (Adulto, Adulto più anziano)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
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.
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Triplicare
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Comparatore attivo: Liraglutide
|
Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
Altri nomi:
|
|
Comparatore placebo: Iniezione salina
|
Placebo injection of 1.8mg saline once daily for 6-months
|
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Glycemic Control Measured by HbA1c
Lasso di tempo: 6-months
|
HbA1c (%)
|
6-months
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Pancreatic and Hepatic Triglyceride Content
Lasso di tempo: 6-months
|
Liver Triglyceride and Pancreatic Triglyceride
|
6-months
|
|
Weight
Lasso di tempo: 6-months
|
6-months
|
|
|
Beta-Cell Function
Lasso di tempo: 6-months
|
Fasting Glucose as a Measure of Beta-Cell Function
|
6-months
|
|
Glucagon
Lasso di tempo: 6-months
|
Measured during mixed meal challenge test.
|
6-months
|
|
Total Daily Insulin Dose
Lasso di tempo: 6-months
|
The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.
|
6-months
|
|
Number of Daily Injections
Lasso di tempo: 6-months
|
The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.
|
6-months
|
|
Blood Pressure
Lasso di tempo: 6-months
|
6-months
|
|
|
Lipid Profile
Lasso di tempo: 6-months
|
6-months
|
|
|
Liver Function Blood Test
Lasso di tempo: 6-months
|
6-months
|
|
|
Hypoglycemic Events
Lasso di tempo: 6-months
|
Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl
|
6-months
|
|
Quality of Life Survey (QoL) - General Health Perception
Lasso di tempo: 6-months
|
General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor.
|
6-months
|
|
Beta-Cell Function
Lasso di tempo: 6 months
|
Fasting C-peptide as a Measure of Beta-Cell Function
|
6 months
|
|
Matsuda Index as a Measure of Beta Cell Function
Lasso di tempo: 6 months
|
The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values.
Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)).
Higher/lower values = better/worse insulin sensitivity.
|
6 months
|
|
Beta-cell Function
Lasso di tempo: 6 Months
|
AUC c-peptide
|
6 Months
|
|
Ratio (AUC C-peptide/AUC Glucose)
Lasso di tempo: 6 months
|
6 months
|
|
|
AUC Glucose
Lasso di tempo: 6 months
|
6 months
|
|
|
Quality of Life Survey (QoL) - Current Health Perception
Lasso di tempo: 6 months
|
Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.
|
6 months
|
|
Quality of Life Survey (QoL) - Treatment Satisfaction
Lasso di tempo: 6 months
|
Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
|
6 months
|
|
Quality of Life Survey (QoL) - Treatment Impact
Lasso di tempo: 6 months
|
Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.
|
6 months
|
|
Quality of Life Survey (QoL) - Social or Vocational Worry
Lasso di tempo: 6 months
|
Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.
|
6 months
|
|
Quality of Life Survey (QoL) - Hypoglycemia Fear
Lasso di tempo: 6 months
|
Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry.
|
6 months
|
|
Quality of Life Survey (QoL) - Glycemia Control Perception
Lasso di tempo: 6 months
|
Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.
|
6 months
|
|
Quality of Life Survey (QoL) - Lifestyle Flexibility
Lasso di tempo: 6 months
|
Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.
|
6 months
|
|
Quality of Life Survey (QoL) - Social Stigma
Lasso di tempo: 6 months
|
Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.
|
6 months
|
|
Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment
Lasso di tempo: 6 months
|
Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.
|
6 months
|
|
Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment
Lasso di tempo: 6 months
|
Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire.
This questionnaire addresses several areas with respect to diabetes QoL.
Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.
|
6 months
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Ildiko Lingvay, MD, UT Southwestern
Pubblicazioni e link utili
La persona responsabile dell'inserimento delle informazioni sullo studio fornisce volontariamente queste pubblicazioni. Questi possono riguardare qualsiasi cosa relativa allo studio.
Pubblicazioni generali
- 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.
- Vanderheiden A, Harrison LB, Warshauer JT, Adams-Huet B, Li X, Yuan Q, Hulsey K, Dimitrov I, Yokoo T, Jaster AW, Pinho DF, Pedrosa I, Lenkinski RE, Pop LM, Lingvay I. Mechanisms of Action of Liraglutide in Patients With Type 2 Diabetes Treated With High-Dose Insulin. J Clin Endocrinol Metab. 2016 Apr;101(4):1798-806. doi: 10.1210/jc.2015-3906. Epub 2016 Feb 24.
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 gennaio 2012
Completamento primario (Effettivo)
1 giugno 2016
Completamento dello studio (Effettivo)
1 giugno 2016
Date di iscrizione allo studio
Primo inviato
4 gennaio 2012
Primo inviato che soddisfa i criteri di controllo qualità
5 gennaio 2012
Primo Inserito (Stima)
6 gennaio 2012
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
16 gennaio 2018
Ultimo aggiornamento inviato che soddisfa i criteri QC
15 dicembre 2017
Ultimo verificato
1 dicembre 2017
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
Altri numeri di identificazione dello studio
- IIS-000235
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .