Clinical trial NCT01621308: Intraperitoneal vs Subcutaneous Insulin Administration in Type 1 Diabetes Mellitus
Official title: Intraperitoneal Insulin Administration as Alternative for Intensive Subcutaneous Insulin Therapy in Patients With Type 1 Diabetes Mellitus.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Type 1 Diabetes Mellitus
Keywords: Diabetes Mellitus type 1
Intraperitoneal insulin administration
Subcutaneous insulin administration
Continuous intraperitoneal insulin infusion
Lead sponsor: Medical Research Foundation, The Netherlands
Sponsor class: OTHER
First posted: 2012-06-18
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study sample consists of the subjects on CIPII, who participated in the crossover study performed by Logtenberg et al. (Diabetes Care 32:1372-1377, 2009) or subjects who already used CIPII at that moment (so, for a minimum of 4 years), and matched controls on SC insulin treatment .

The inclusion and exclusion criteria of the previous study are described in detail in (Diabetes Care 32:1372-1377, 2009). In brief, it consisted of patients with T1DM, low fasting c-peptide concentrations (\<0.20 nmol/L), aged 18 to 70 years, treated with MDI or CSII and intermediate or poor glycaemic control; defined as glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mol) and/or ≥5 incidents of hypoglycaemia (\< 4.0mmol/L) per week.

If subjects are on SC insulin, they must be able to 'function' as matched control for CIPII patients. The matching procedure, based on age and gender, will take place after patients are being included in the current study.

Brief summary: Almost all patients with type 1 diabetes mellitus (T1DM) need insulin treatment permanently. For selected patients who are unable to achieve glycaemic targets with subcutaneous (SC) insulin treatment, continuous intraperitoneal (IP) insulin infusion is an third-line alternative.

Previous studies demonstrate that continuous intraperitoneal insulin infusion (CIPII) using an implantable pump device improves glycaemic control and quality of life in patients with 'brittle' T1DM. Nevertheless, literature comparing IP and SC insulin treatment is scarce.

The primary objective of this study is to compare the effects of IP insulin delivery to SC insulin delivery.The null hypothesis (H0) of the current study holds inferiority of CIPII compared to SC insulin regarding long-term glycaemic control. The alternative hypothesis (H1) is the inverse: CIPII is non-inferior to SC insulin. In summary, H0: CIPII is inferior to the SC insulin treatment H1: CIPII is not inferior to SC insulin treatment

This is an investigator initiated, open label and prospective matched-control study with a non-inferiority design. The trial duration is 36 weeks and is conducted in a single-centre (Isala Clinics, Zwolle). If non-inferiority is established superiority analyses are performed.


Eligibility criteria: Case inclusion criteria

* T1DM
* If subjects are on CIPII, they must be included in (8) or
* If subjects are on CIPII, and didn't participate in (8), they must been on CIPII at start of the previous study (8)
* If subjects are on CIPII, they must been on CIPII for the past 4 years without interruptions (\>30 days)
* Proper knowledge of the Dutch language.

Case exclusion criteria

* Impaired renal function (plasma creatinine ≥150 µmol/L or glomerular filtration rate as estimated by the Cockcroft-Gault formula ≤50ml/min)
* Cardiac problems (unstable angina or myocardial infarction within the previous 12 months or New York Heart Association class III or IV congestive heart failure
* Mentally handicapped
* Current or past psychiatric treatment for schizophrenia
* Cognitive or bipolar disorder
* Current use or oral corticosteroids or suffering from a condition which necessitated oral or systemic corticosteroids use more than once in the previous 12 months
* Substance abuse, other than nicotine
* Current gravidity or plans to become pregnant during the trial
* Plans to engage in activities that require going \>25 feet below sea level
* Any condition that the investigator and/or coordinating investigator feels would interfere with trial participation or evaluation of results.

4.4 Control inclusion criteria

* T1DM
* SC insulin as mode of insulin administration
* If subjects are on SC insulin, they must been on SC insulin for the past 4 years without interruption (\>30 days)
* HbA1c at time of matching must be ≥7.0% (53mmol/mol)
* Proper knowledge of the Dutch language.

Control exclusion criteria

* Impaired renal function (plasma creatinine ≥150 µmol/L or glomerular filtration rate as estimated by the Cockcroft-Gault formula ≤50ml/min)
* Cardiac problems (unstable angina or myocardial infarction within the previous 12 months or New York Heart Association class III or IV congestive heart failure
* Mentally handicapped
* Current or past psychiatric treatment for schizophrenia
* Cognitive or bipolar disorder
* Current use or oral corticosteroids or suffering from a condition which necessitated oral or systemic corticosteroids use more than once in the previous 12 months
* Substance abuse, other than nicotine
* Current gravidity or plans to become pregnant during the trial
* Plans to engage in activities that require going \>25 feet below sea level
* Any condition that the investigator and/or coordinating investigator feels would interfere with trial participation or evaluation of results.

Primary outcomes:
measure: glycaemic regulation
timeFrame: 6 months
Secondary outcomes:
measure: Percentage time spent in hypo/hyper- and euglycaemia during a 3-7 day 24-hour blood glucose profile using a continuous glucose measurement system (CGMS).
timeFrame: 6 months
measure: Hypoglycaemic episodes
timeFrame: 6 months
measure: Concentrations of IGF-1 and IGFBP
timeFrame: 6 months
measure: Total daily insulin dose.
timeFrame: 6 months
measure: Lipid spectrum
timeFrame: 6 months
measure: Health related quality of life
timeFrame: 6 months
measure: Diabetes related quality of life
timeFrame: 6 months
measure: Diabetes related distress
timeFrame: 6 months
measure: Diabetes related self care
timeFrame: 6 months
measure: Treatment satisfaction
timeFrame: 6 months
measure: body mass index
timeFrame: 6 months
measure: Blood pressure
timeFrame: 6 months
measure: Microvascular complications of diabetes
timeFrame: 6 months
measure: Macrovascular complications of diabetes
timeFrame: 6 months
Other outcomes:
Locations:
city: Meppel
country: Netherlands
facility: Diaconessenhuis Hospital
state: Drenthe
city: Zwolle
country: Netherlands
facility: Isala clinics
state: Overijssel
Study officials:
affiliation: Isala clinics, Diabetes centre
name: Henk JG Bilo, MD PhD FRCP
role: STUDY_CHAIR
affiliation: Isala clinics, Diabetes centre
name: Peter R Dijk, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Isala clinics, Diabetes centre
name: N Kleefstra, M.D. PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Isala clinics, Diabetes centre; University Medical Centre Groningen dept. of internal medicine
name: S JJ Logtenberg, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Isala clinics, Diabetes centre; University Medical Centre Groningen dept. of primary medicine
name: Klaas H Groenier, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Logtenberg SJ, Kleefstra N, Houweling ST, Groenier KH, Gans RO, van Ballegooie E, Bilo HJ. Improved glycemic control with intraperitoneal versus subcutaneous insulin in type 1 diabetes: a randomized controlled trial. Diabetes Care. 2009 Aug;32(8):1372-7. doi: 10.2337/dc08-2340. Epub 2009 May 8.
citation: van Dijk PR, Logtenberg SJ, Chisalita SI, Hedman CA, Groenier KH, Gans RO, Kleefstra N, Arnqvist HJ, Bilo HJ. Different Effects of Intraperitoneal and Subcutaneous Insulin Administration on the GH-IGF-1 Axis in Type 1 Diabetes. J Clin Endocrinol Metab. 2016 Jun;101(6):2493-501. doi: 10.1210/jc.2016-1473. Epub 2016 Apr 26.
citation: van Dijk PR, Logtenberg SJ, Hendriks SH, Groenier KH, Feenstra J, Pouwer F, Gans RO, Kleefstra N, Bilo HJ. Intraperitoneal versus subcutaneous insulin therapy in the treatment of type 1 diabetes mellitus. Neth J Med. 2015 Nov;73(9):399-409.