Insulin in Total Parenteral Nutrition (INSUPAR)

Subcutaneous Versus Intravenous Basal Insulin in Non-critical Hospitalized Diabetic Patients That Receive Total Parenteral Nutrition

Analyze the level of metabolic control achieved with a routine of regular insulin in the parenteral nutrition (PN) reservoir in addition to subcutaneous glargine insulin, versus only regular insulin in the PN reservoir.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus
• Intervention / Treatment: Drug: Subcutaneous glargine insulin; Drug: Regular insulin added to TPN bag

Detailed Description

A pattern of basal insulin (using subcutaneous insulin glargine and regulating the stock as prandial), plus regular subcutaneous insulin as rescue, applied to total parenteral nutrition (TPN) should be as effective (glycemic control, variability) and safe (hypoglycemia) as the usual (regular insulin inside the TPN reservoir and subcutaneous insulin as rescue) in patients with type 2 diabetes critics.

• Study Type: Interventional
• Enrollment (Actual): 163
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Albacete, Spain, 02008
    • Complejo Hospitalario Universitario de Albacete
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Badajoz, Spain, 06080
    • Hospital Universitario Infanta Cristina
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08907
    • Hospital Universitario Bellvitge
  • Barcelona, Spain, 08970
    • Hospital de Sant Joan Despi Moisès Broggi (Consorci Sanitari Integral)
  • Córdoba, Spain, 14006
    • Hospital Universitario Reina Sofia
  • Guadalajara, Spain, 19002
    • Hospital Universitario de Guadalajara
  • Jaén, Spain, 23008
    • Complejo Hospitalario de Jaen
  • León, Spain, 24008
    • Complejo Asistencial Universitario de Leon
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28040
    • Hospital Clinico San Carlos
  • Madrid, Spain, 28007
    • Hospital Universitario Gregorio Maranon
  • Málaga, Spain, 29009
    • Hospital Regional Universitario de Málaga
  • Málaga, Spain, 29010
    • Hospital Universitario Virgen de la Victoria
  • Sevilla, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Tenerife, Spain, 38010
    • Hospital Universitario Nuestra Señora de la Candelaria
  • Valencia, Spain, 46026
    • Hospital Universitario y Politécnico La Fe
  • Valladolid, Spain, 47003
    • Hospital Clinico Universitario de Valladolid
  • Zaragoza, Spain, 50009
    • Hospital Clinico Universitario Lozano Blesa
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • A Coruña
    • Ferrol, A Coruña, Spain, 15405
      • Hospital Arquitecto Marcide-Naval
  • Asturias
    • Gijón, Asturias, Spain, 33394
      • Hospital de Cabuenes
  • Badajoz
    • Mérida, Badajoz, Spain, 06800
      • Hospital de Mérida
  • Baleares
    • Palma de Mallorca, Baleares, Spain, 07198
      • Hospital Son Llatzer
  • Ciudad Real
    • Alcázar de San Juan, Ciudad Real, Spain, 13600
      • Hospital General Mancha Centro
  • Madrid
    • Alcalá de Henares, Madrid, Spain, 28805
      • Hospital Universitario Príncipe de Asturias
    • Fuenlabrada, Madrid, Spain, 28942
      • Hospital Universitario de Fuenlabrada
    • Leganés, Madrid, Spain, 28911
      • Hospital Universitario Severo Ochoa
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Universitario Puerta de Hierro
  • Murcia
    • El Palmar, Murcia, Spain, 30150
      • Hospital Clinico Universitario Virgen de la Arrixaca
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Complejo Hospitalario de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults (>18 years)
• Previously diagnosed with diabetes mellitus.
• Hospitalized but without intensive cares.
• Have indication of total parenteral nutritional support (TPN, meaning the covering over 70% of the estimated daily requirements intravenously) for a minimum of 5 days.
• Signature of informed consent.

Exclusion Criteria:

• Diabetes mellitus type 1, diabetes secondary to total pancreatectomy.
• Patients with intensive cares.
• Patients who have been prescribed TPN in intensive cares unity more than 48 hours before admission to hospitalization.
• Intradialytic parenteral nutrition.
• Patients under 18 or pregnant women.
• Patients with renal insufficiency stage 3 B (glomerular filtration rate < 45 mL / min).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Glargine insulin; Single dose glargine insulin (basal component) + regular insulin within total parenteral nutrition (TPN) reservoir (prandial component). 50% of the total calculated dose of insulin is administered subcutaneously as single dose subcutaneous glargine insulin; remaining 50% of the total calculated dose of insulin is administered as regular insulin in the TPN reservoir. Interventions used: Intravenous glargine insulin, and regular insulin added to TPN bag	Drug: Subcutaneous glargine insulin; Glargine insuline is an insulin analogue which has a prolonged duration of action. Insulin glargine is obtained by recombinant DNA technology in Escherichia coli.; Other Names: Lantus®; Abasaglar®; ATC code A10AE0; Drug: Regular insulin added to TPN bag; Regular insulin is human insulin produced in Saccharomyces cerevisiae by recombinant DNA technology.; Other Names: ATC code A10AB01; Actrapid®
Active Comparator: Regular insulin; Regular insulin added to TPN bag (basal + prandial component). The calculated total dose of insulin is administered as regular insulin in the TPN reservoir. Interventions used: Regular insulin added to TPN bag	Drug: Regular insulin added to TPN bag; Regular insulin is human insulin produced in Saccharomyces cerevisiae by recombinant DNA technology.; Other Names: ATC code A10AB01; Actrapid®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Basal blood glucose value before starting TPN	Basal glucose value before starting TPN (in mg/dL).	Before starting total parenteral nutrition
Periodical blood glucose	All blood glucose values (in mg/dL) every 6 hours during 15 days of TPN infusion.	Every 6h during 15 days of treatment
Variation of average blood glucose compared with total dose of insulin	Variation of average glucose (in mg/dL) compared with total dose of insulin (in mL), in days 1, 5 and 15 of treatment.	In days 1, 5 and 15 of treatment
Number of hypoglycaemia	Number of symptomatic and asymptomatic hypoglycaemia with blood glucose below 70 mg/dL during TPN treatment up to 15 days.	During TPN treatment up to 15 days
Number of severe hypoglycaemia	Number of symptomatic and asymptomatic hypoglycaemia with blood glucose below 40 mg/dL during TPN treatment up to 15 days.	During TPN treatment up to 15 days
Hypoglycemia blood glucose values	If the patient refers typical symptoms of hypoglycemia, a measure of blood glucose (in mg/mL) is immediately taken to check the level	Through study completion, an average of 15 days.
Hypoglycemia symptoms	If blood glucose <70 mg / dL, it is recorded whether or not the patient has symptoms consistent with hypoglycemia and how the episode terminates	Through study completion, an average of 15 days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Standard deviation of blood glucose	Standard deviation of blood glucose (SD): Expressed in milligrams per deciliter (in mg/dL).	At day 15 of treatment
Blood glucose coefficient of variation (CV)	Coefficient of variation (CV): Expressed as a percentage (%). The ratio of the standard deviation of the blood glucoses values (in mg/dL) and the average blood glucose (in mg/dL), multiplied by 100.	At day 15 of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infections related with catheter used in parenteral nutrition	Investigator asses the occurrence of infectious complications in parenteral nutrition catheter. For the evaluation of the infections, temperature is collected daily and patient will perform a blood test weekly. It will be suspected infectious complication for any sudden onset of fever (usually "peaks"), with no other apparent source of infection.	At day 15 of treatment
Hypertriglyceridemia	A determination above this value will be considered a complication: Hypertriglyceridemia ≥500 mg/dL	Every 6h during 15 days of treatment.
Hypernatremia	A determination above this value will be considered a complication: Hypernatremia >150 mEq/L	Every 6h during 15 days of treatment.
Hyponatremia	A determination below this value will be considered a complication: Hyponatremia <135 mEq/L	Every 6h during 15 days of treatment.
Hypokalemia	A determination below this value will be considered a complication: Hypokalemia <3 mEq/L	Every 6h during 15 days of treatment.
Hypomagnesemia	A determination below this value will be considered a complication: Hypomagnesemia <1.2 mg/dL	Every 6h during 15 days of treatment.
Hypophosphatemia	A determination below this value will be considered a complication: Hypophosphatemia <2 mg/dL	Every 6h during 15 days of treatment.
Hyperchloremia	A determination above this value will be considered a complication: Hyperchloremia >120 mEq/L	Every 6h during 15 days of treatment.
Hypocalcemia corrected calcium	A determination below this value will be considered a complication: Hypocalcemia corrected calcium <8 mg/dL	Every 6h during 15 days of treatment.
Alteration of liver function markers	Alteration of liver function markers is defined as an elevation twice higher than normal limits, according to each laboratory, of two of some of the following parameters (when previously normal): GGT, GOT, GPT, FA or total bilirubin, at least 7 days after initiating TPN.	At day 7 and 15 of treatment
Adverse events	All adverse events (AEs) are recorded in the case report data since the moment when the patient signs the informed consent. These events will be defined following the organ classification database of MedDRA system.	At day 15 of treatment

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza Progreso y Salud
• Investigators: Principal Investigator: Gabriel Olveira Fuster, PhD, Hospital Regional de Malaga

Publications and helpful links

General Publications

• Olveira G, Abuin J, Lopez R, Herranz S, Garcia-Almeida JM, Garcia-Malpartida K, Ferrer M, Cancer E, Luengo-Perez LM, Alvarez J, Aragon C, Ocon MJ, Garcia-Manzanares A, Breton I, Serrano-Aguayo P, Perez-Ferre N, Lopez-Gomez JJ, Olivares J, Arraiza C, Tejera C, Martin JD, Garcia S, Abad AL, Alhambra MR, Zugasti A, Parra J, Torrejon S, Tapia MJ. Regular insulin added to total parenteral nutrition vs subcutaneous glargine in non-critically ill diabetic inpatients, a multicenter randomized clinical trial: INSUPAR trial. Clin Nutr. 2020 Feb;39(2):388-394. doi: 10.1016/j.clnu.2019.02.036. Epub 2019 Mar 20.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): March 31, 2018
• Study Completion (Actual): April 4, 2018

Study Registration Dates

• First Submitted: February 16, 2016
• First Submitted That Met QC Criteria: March 7, 2016
• First Posted (Estimate): March 11, 2016

Study Record Updates

• Last Update Posted (Actual): May 24, 2018
• Last Update Submitted That Met QC Criteria: May 22, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Keywords: insulin; total parenteral nutrition; glargine insulin
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Glargine
• Other Study ID Numbers: FPS-INSUPAR-2015-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes