Intensive Insulin Treatment and Ischemic Foot Ulcer

• Sponsor: Karolinska Institutet (Other)
• Overall Status: Completed
• CT.gov ID: NCT01957930
• Collaborator: (none)
• Enrollment: 91
• Locations: 2
• Arms: 3
• Duration (Months): 353
• Patients Per Site: 45.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

We aim to investigate the relationship between skin microvascular function and the first hospitalization for ischemic foot ulcer in patients with type 1 diabetes former randomized during 7.5 years to intensified conventional insulin treatment (ICT) compared to standard insulin treatment (ST).

Condition or Disease	Intervention/Treatment	Phase
Ischemic Foot Ulcer	Drug: Intensified insulin treatment; Drug: Standard treatment	N/A

Detailed Description

The Stockholm Diabetes Intervention Study (SDIS) aimed to determine whether intensified insulin treatment were feasible and led to less serious diabetic complications. 102 patients with type 1 diabetes mellitus were randomiz (October 1982 to March 1984) to intensified conventional treatment (ICT; n=48) or standard treatment (ST; n=54). The randomized SDIS study lasted for 7.5 years, whereas 96 patients were fully evaluated. Thereafter patients were assigned to their regular clinical visits.

In the present study, 96 patients from the SDIS study were asked to participate in current study and to investigate their skin microcirculation, in which 72 patients agreed (ICT; n=35 vs. ST; n=37). Also, nineteen healthy subjects participated as controls for the method of iontophoresis, with no intention to be followed-up. Exclusions criteria were; any history or ongoing ischemic foot ulcer or peripheral artery disease or osteoartropathy. The iontophoresis investigation took place 5.5 years ± 2 months, after the primary randomization ceased (7.5 years). All participants (except the control subjects) were then followed-up until first time hospitalization for ischemic foot ulcer or until 31 december 2011.

Study Design

• Study Type: Interventional
• Actual Enrollment: 91 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intensified Insulin Treatment and Skin Microcirculation; Its Relation to Ischemic Foot Ulcer in Patients With Type 1 Diabetes Mellitus: A Long-term Follow-up Study
• Study Start Date: Jan 1, 1984
• Actual Primary Completion Date: Dec 1, 2011
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intensified insulin treatment Basal (Monotard) insulin; ones a day Bolus (Actrapid) insulin; thrice a day	Drug: Intensified insulin treatment; The treatment regimen of the intensified treatment group consisted of individual education and then continuous tutoring with frequent face-to-face and telephone contact.; Other Names: Monotard; Actrapid
Active Comparator: Standard treatment Mixed Insulin (2-3 times a day)	Drug: Standard treatment; Patients continuing with routine diabetes care (insulin treatment), visiting physician every four months; Other Names: Premixed Insulin
No Intervention: Healthy controls These people were solely controls for the iontophoresis method used in the study. With no intervention or follow-up-

Outcome Measures

Primary Outcome Measures

1. Ischemic Foot Ulcer [Until hospitalization for ischemic foot ulcer or until 31 December 2011]

   The study outcome is the first hospitalization for ischemic foot ulcer, defined by the ICD-10 discharge code

Other Outcome Measures

1. Microvascular Endothelial Function [7 years]

   Microvascular function is measured with a single point iontophoresis after stimulation with topically applied acetylcholine (ACh) [endothelial-dependent], sodium nitroprusside (SNP) [endothelial-independent], and capsaicin [C-nociceptive dependent] vasculature response.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Born 1930 or later, Type 1 diabetes appearing at age 30 or earlier and with insulin dependency within 1 year from diagnosis, no known abuse of alcohol or drugs, non-prolipherative retinopathy of any degree present, no previous photocoagulation, normal serum creatinine, unsatsifactory blood glucose control according to the physician in charge of the patients.

Exclusion Criteria:

Any history or ongoing ischemic foot ulcer,or peripheral artery disease,or osteoartropathy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Karolinska Institutet, Department of Clinical Science and Education, Södersjukhuset	Stockholm		Sweden	118 83
2	Karolinska Institutet, Division of Internal Medicine Södersjukhuset AB	Stockholm		Sweden	118 83

Sponsors and Collaborators

• Karolinska Institutet

Investigators

• Principal Investigator: Thomas Nyström, MD, Karolinska Institutet

Study Documents (Full-Text)

None provided.

More Information

Publications

• Reichard P, Britz A, Cars I, Nilsson BY, Sobocinsky-Olsson B, Rosenqvist U. The Stockholm Diabetes Intervention Study (SDIS): 18 months' results. Acta Med Scand. 1988;224(2):115-22.
• Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term intensified insulin treatment on the development of microvascular complications of diabetes mellitus. N Engl J Med. 1993 Jul 29;329(5):304-9.

• Responsible Party: Thomas Nystrom, MD, PhD, Karolinska Institutet
• ClinicalTrials.gov Identifier: NCT01957930
• Other Study ID Numbers: EPI-2012
• First Posted: Oct 8, 2013
• Last Update Posted: Sep 29, 2020
• Last Verified: Sep 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Thomas Nystrom, MD, PhD, Karolinska Institutet: HbA1c; Iontophoresis; Intensified insulin treatment; Ischemic foot ulcer; Type 1 diabetes
• Additional relevant MeSH terms: Foot Ulcer; Ischemia; Ulcer; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Arm/Group Title	Intensified Insulin Treatment	Standard-treatment	Healthy Controls
Arm/Group Description	Intensified conventional insulin treatment: The treatment regimen of the intensified treatment group consisted of individual education and then continuous tutoring with frequent face-to-face and telephone contact.	Continuing with routine diabetes care Standard treatment: Patients continuing with routine diabetes care (insulin treatment), visiting physician every four months	19 healthy controls were invited to compare microcirculation between healthy and diabetes individuals
Period Title: Overall Study
STARTED	35	37	19
COMPLETED	35	37	19
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Intensified Insulin Treatment	Standard-treatment	Healthy Control	Total
Arm/Group Description	Intensified conventional insulin treatment: The treatment regimen of the intensified treatment group consisted of individual education and then continuous tutoring with frequent face-to-face and telephone contact.	Continuing with routine diabetes care Standard treatment: Patients continuing with routine diabetes care (insulin treatment), visiting physician every four months	Solely controls for the iontophoresis method and no intention to be followd-up.	Total of all reporting groups
Overall Participants	35	37	19	91
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	35 100%	37 100%	19 100%	91 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	42	42	38	42
Sex: Female, Male (Count of Participants)
Female	21 60%	22 59.5%	8 42.1%	51 56%
Male	14 40%	15 40.5%	11 57.9%	40 44%
Region of Enrollment (participants) [Number]
Sweden	35 100%	37 100%	19 100%	72 79.1%

Outcome Measures

1. Primary Outcome

Title	Ischemic Foot Ulcer
Description	The study outcome is the first hospitalization for ischemic foot ulcer, defined by the ICD-10 discharge code
Time Frame	Until hospitalization for ischemic foot ulcer or until 31 December 2011

Outcome Measure Data

Analysis Population Description

Data for Healthy Controls was not collected for this Outcome Measure.

Arm/Group Title	Intensified Insulin Treatment	Standard-treatment
Arm/Group Description	Intensified conventional insulin treatment: The treatment regimen of the intensified treatment group consisted of individual education and then continuous tutoring with frequent face-to-face and telephone contact.	Continuing with routine diabetes care Standard treatment: Patients continuing with routine diabetes care (insulin treatment), visiting physician every four months
Measure Participants	35	37
Number [participants]	3 8.6%	10 27%

2. Other Pre-specified Outcome

Title	Microvascular Endothelial Function
Description	Microvascular function is measured with a single point iontophoresis after stimulation with topically applied acetylcholine (ACh) [endothelial-dependent], sodium nitroprusside (SNP) [endothelial-independent], and capsaicin [C-nociceptive dependent] vasculature response.
Time Frame	7 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	Intensified Insulin Treatment		Standard-treatment		Healthy Controls
Arm/Group Description	Intensified conventional insulin treatment: The treatment regimen of the intensified treatment group consisted of individual education and then continuous tutoring with frequent face-to-face and telephone contact.		Continuing with routine diabetes care Standard treatment: Patients continuing with routine diabetes care (insulin treatment), visiting physician every four months		These people were solely controls for the iontophoresis method used in the study. With no intervention or follow-up.
All Cause Mortality
	Intensified Insulin Treatment		Standard-treatment		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Intensified Insulin Treatment		Standard-treatment		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/37 (0%)		0/19 (0%)
Blood and lymphatic system disorders
0	0/35 (0%)	0	0/37 (0%)	0	0/19 (0%)	0
Other (Not Including Serious) Adverse Events
	Intensified Insulin Treatment		Standard-treatment		Healthy Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/35 (0%)		0/37 (0%)		0/19 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.