INSPIRE Diabetes Study: Basal Bolus Insulin as Primary Treatment of Type 2 Diabetes

This study has been completed.
Sponsor:
Collaborator:
Western University of Health Sciences
Information provided by (Responsible Party):
Jay Shubrook, Ohio University
ClinicalTrials.gov Identifier:
NCT01087567
First received: March 15, 2010
Last updated: April 16, 2014
Last verified: April 2014
  Purpose

T2DM has become an American Epidemic. Currently 8% of the US population has diabetes and rates may be as high as 33% by the year 2050 (1). Although there are many treatment options for people with T2DM, none have been proven in humans to prevent the defects in insulin secretion (2) and insulin action (3) and beta cell dysfunction (4) that result with very high glucose levels and typically worsen as the disease progresses. Any treatment that could delay the progression of pancreatic beta cell failure (as measured by the need for rescue therapy with oral agents) would be a significant advancement in diabetes treatment.

Insulin therapy is appropriate at any point in T2DM disease progression, but it is commonly only used as a rescue therapy after failure of oral therapies. A number of outpatient insulin titration protocols have been shown to be safe and effective and speed patient's ability to gain glucose control (5-8). Recent studies have shown that initiation of insulin at onset of T2DM is beneficial at achieving early and long-term glucose control (6-9). However these protocols have used intravenous human insulin in the in-patient setting, continuous subcutaneous insulin by insulin pump or older human insulins in the out-patient setting. Many of these protocols are unlikely to be utilized in routine patient care. To date, no "insulin first" studies have been published with analog insulins in an outpatient basal-bolus regimen with patient driven titration.


Condition Intervention Phase
Type 2 Diabetes
Drug: Intensive insulin
Drug: Routine Care
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Intensive Insulin Regimen as a Primary Treatment of New Onset of Type 2 DM

Resource links provided by NLM:


Further study details as provided by Ohio University:

Primary Outcome Measures:
  • The need for rescue therapy [ Time Frame: at 3 months ] [ Designated as safety issue: No ]
  • The need for rescue therapy [ Time Frame: at 6 months ] [ Designated as safety issue: No ]
  • The need for rescue therapy [ Time Frame: at 9 months ] [ Designated as safety issue: No ]
  • The need for rescue therapy [ Time Frame: at 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • A1c,C-peptide. Time to normoglycemia and rescue therapy. Mean glucose, mean FBG, HOMA-B, HOMA-IR. Hypoglycemic events (minor and major. Tolerability based on side effects. [ Time Frame: 3 months, 6 months, 9 months, 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 23
Study Start Date: July 2010
Study Completion Date: January 2014
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intensive insulin regimen
A weight based, basal bolus will be given for 12 weeks.
Drug: Intensive insulin
A weight-based basal bolus insulin regimen starting with 0.1 units/kg/day of Glargine and 4 units/meal of Glulisine.
Other Names:
  • Lantus Insulin
  • Apidra Insulin
Active Comparator: Routine Care
Routine Care patients receive oral medications based upon the 2009 ADA treatment recommendations: Metformin, Glimepiride, Pioglitazone.
Drug: Routine Care
Treatment in routine care will be based upon the 2009 ADA treatment recommendations.
Other Names:
  • Metformin
  • Glimepiride
  • Pioglitazone

Detailed Description:

Insulin, when used as an initial treatment of T2DM, has a great potential to produce glucose control faster than any other treatment regimen. However, it is typically used as the treatment of last resort in T2DM. In this study, the investigators offer a novel approach to use insulin as the initial therapy in new-onset T2DM with the aim of determining its efficacy toward producing lasting glucose control.

Hypothesis: Treating newly diagnosed T2DM patients with insulin therapy versus standard of care for a short period of time will lead to improvement in glycemic control that is durable beyond the length of time taking the insulin and it may improve beta cell function.

Primary endpoints: Time to need rescue therapy, Need for rescue therapy at all time points. A1C change at 3, 6, 9 and 12 months.

Secondary endpoints: Mean glucose and mean fasting glucose at 3, 6, 12 months. C-peptide, HOMA-B, HOMA-IR, A1C the same time points, OGTT at week 12 and 56. Total number of hypoglycemic events (minor and major) and tolerability based on side effects.

Treatment arm: Weight based protocol of insulin Glargine and Glulisine. Control arm: oral medications per ADA 2009 recommended treatment algorithm. Rescue group available for both arms after initial 12 weeks.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Newly diagnosed T2DM (≤ 6 months since diagnosis)
  • Drug naïve (less than 2 weeks of insulin and OHAs)
  • A1C ≥ 8%
  • Age ≥ 18 years
  • Normal to high baseline C-peptide (≥ 0.5 ug/dL)
  • FBG > 180 mg/dL, A1C > 8%.

Exclusion Criteria:

  • Pregnancy
  • Clinically evident heart failure
  • Nephrotic syndrome
  • Allergy to insulin or any of the oral medications in the study
  • Presence of anti-GAD antibodies
  • Islet cell antibodies
  • Anti-insulin antibodies
  • Any physical disabilities that would preclude self-administration of injectable insulin.
  • Evidence of hypoglycemia during screening phase.
  • History of lactic acidosis, allergy to metformin or history of chronic renal disease or a serum creatinine > 1.5 in men or > 1.4 in women
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01087567

Locations
United States, Ohio
Ohio University
Athens, Ohio, United States, 45701
Sponsors and Collaborators
Ohio University
Western University of Health Sciences
Investigators
Principal Investigator: Jay H Shubrook, D.O. Ohio University
  More Information

Publications:
Responsible Party: Jay Shubrook, Associate Professor, Ohio University
ClinicalTrials.gov Identifier: NCT01087567     History of Changes
Other Study ID Numbers: 16037
Study First Received: March 15, 2010
Last Updated: April 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Ohio University:
diabetes
insulin
rescue therapy

Additional relevant MeSH terms:
Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Pioglitazone
Insulin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014