- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01055223
Fracture Risk With Thiazolidinediones
The Association Between Exposure to Spironolactone or Amiloride and Fracture Risk Among Subjects Treated With Thiazolidinediones
Treatment with thiazolidinediones (TZD) has recently been reported to possibly increase the risk of fractures in a randomized trial exploring the efficacy of rosiglitazone (RSG), metformin, or glyburide encompassing 4360 patients with type 2 diabetes.
It is hypothesized that spironolactone, a diuretic that is broadly used for the treatment of fluid retention and edema associated with TZD, has a potential protective effect against bone fractures. However, to our knowledge, this has not been tested in diabetic patients treated with TZD. Amiloride is another diuretic that shares with spironolactone the anti mineralocorticoid ion gated channels activity and will be analysed in this study with regard to possible protective effect against bone fracture in combination with TZD.
This study is a nested case-control study conducted among type 2 diabetes subjects exposed to TZD. The study aims to explore if the risk of fracture is reduced among type 2 diabetic subjects exposed to spironolactone and TZD. The study will compare the odds of any low impact fracture, and hand, foot, upper arm, wrist, and hip fracture incidence in subjects treated with TZD+spironolactone and TZD+amiloride compared to subjects treated with TZD only.
The study population will consist of type 2 diabetes patients aged 18 -65 years old exposed to TZD. To be eligible for the study, a subject must have had at least one International Classification of Disease (ICD)-9 code for type 2 diabetes and have at least 6 months or at least 12 months of exposure to TZD (rosiglitazone [RSG], pioglitazone [PIO] or troglitazone) during their follow-up time available in the database.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- At least one ICD-9 code for type 2 diabetes
- At least 6 months or at least 12 months of exposure to TZD (RSG, PIO or troglitazone) during their follow-up time available in the database (The subject's study period begin date will be defined as the earliest date of their first TZD prescription. Subjects included in the study are required to have at least six months of follow-up time in the database prior to their first TZD prescription)
Exclusion Criteria:
- Subjects with a diagnosis of Paget's disease and osteomalacia
- A history of fracture, osteoporosis or cancer prior to the first prescription of TZD (study begin date)
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Type 2 diabetes subjects
|
Drug exposure will be inferred from prescription claims.
Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion.
Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion. In order to be eligible for inclusion in this category, the prescription days supply for TZD and spirinolactone must overlap by at least 30 days. Subjects who have been exposed to TZD for at least 6 months or at least 12 months will be considered for inclusion. In order to be eligible for inclusion in this category, the prescription days supply for TZD and Amiloride must overlap by at least 30 days. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Low Impact Fractures in Males and Females After 6 Months of Exposure to TZD
Time Frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 and December 31, 2008
|
ICD-9 codes (805-807.4x,
808-810.xx,
812-829.xx)
were captured from Uniform Billing-92 records and Health Care Finance Administration records.
Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription).
For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.
|
From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 and December 31, 2008
|
Number of Low Impact Fractures in Males and Females After 12 Months of Exposure to TZD
Time Frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
ICD-9 codes (805-807.4x,
808-810.xx,
812-829.xx)
were captured from Uniform Billing-92 records and Health Care Finance Administration records.
Case is defined as incident cases of fracture with an ICD-9 diagnostic code for any low impact fracture occurring after the study period begin date (earliest date of the first TZD prescription).
For each subject defined as case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched to cases on age (+ 5 years), gender, and year of fracture diagnosis.
|
From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 6 Months of Exposure to TZD
Time Frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
ICD-9 codes (815.0x,
816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records.
Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription).
For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
|
From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
Number of Fractures of the Hand, Foot, Upper Arm, and Wrist in Males and Females After 12 Months of Exposure to TZD
Time Frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
ICD-9 codes (815.0x,
816.0x, 817.0x, 825.0x, 825.2x, 826.0x, 812.0x, 812.2x, 812.4x, 814.0x) were captured from UB-92 records and HCFA 1500 records.
Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hand, foot, upper arm, and wrist fracture after the study period begin date (earliest date of the first TZD prescription).
For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
|
From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
Number of Hip Fractures Combined in Males and Females After 6 Months of Exposure to TZD
Time Frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
ICD-9 codes (820.0x,
820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records.
Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription).
For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
|
From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
Number of Hip Fractures Combined in Males and Females After 12 Months of Exposure to TZD
Time Frame: From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
ICD-9 codes (820.0x,
820.2x, 820.8x) were captured from UB-92 records and HCFA 1500 records.
Case is defined as incident cases of fracture with an ICD-9 diagnostic code for hip fracture after the study period begin date (earliest date of the first TZD prescription).
For each case, up to four controls were randomly selected from patients with type 2 diabetes exposed to TZD without a fracture diagnosis during follow-up and matched on age (+ 5 yrs), gender, and year of fracture diagnosis.
|
From the earliest date of first TZD prescription to the fracture diagnosis date (Cases) or the end of follow-up in the database (Controls) between January 1, 1997 to December 31, 2008
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Glucose Metabolism Disorders
- Metabolic Diseases
- Wounds and Injuries
- Endocrine System Diseases
- Diabetes Mellitus
- Diabetes Mellitus, Type 2
- Fractures, Bone
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Natriuretic Agents
- Membrane Transport Modulators
- Diuretics
- Sodium Channel Blockers
- Hormone Antagonists
- Mineralocorticoid Receptor Antagonists
- Diuretics, Potassium Sparing
- Acid Sensing Ion Channel Blockers
- Epithelial Sodium Channel Blockers
- Spironolactone
- Amiloride
- Troglitazone
Other Study ID Numbers
- 113332
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Fractures, Bone
-
Lawson Health Research InstituteCompleted
-
AO Innovation Translation CenterRecruitingLong Bone FracturesUnited States, Canada, Australia, Ghana, Chile, China, Germany, India, Pakistan, Venezuela, Spain, Croatia, Greece
-
University Hospital, Clermont-FerrandRecruiting
-
IlluminOss Medical, Inc.CompletedHumerus Fracture Metastatic Bone DiseaseUnited States
-
Centre Hospitalier Universitaire Saint PierreRecruiting
-
McMaster UniversityMcMaster Surgical AssociatesCompleted
-
University of UtahCompletedBone Strength | Stress Fractures | Bone Geometry | Biomechanical ChangesUnited States
-
University of British ColumbiaCompleted
-
Novo Nordisk A/SCompletedBone Fracture | Tibia FracturesIsrael, Germany, Finland, Hungary, Spain, South Africa, Norway, France, Poland
-
Lawson Health Research InstituteUnknownBone Fractures | Dislocations
Clinical Trials on TZD only (RSG or PIO or troglitazone)
-
OPKO Health, Inc.CompletedDiabetes Mellitus, Type 2United States
-
Centre Hospitalier Universitaire de NīmesCompletedRhinitis, Allergic | Asthma, AllergicFrance
-
University of HoustonCompletedDepression | Stress | Anxiety | Well-beingUnited States
-
Johns Hopkins Bloomberg School of Public HealthCenters for Medicare and Medicaid ServicesCompletedBreast Cancer | Prostate Cancer | Cervix Cancer | Colon Cancer | Rectum CancerUnited States
-
University of PittsburghNational Institute on Aging (NIA)CompletedInsomniaUnited States
-
University of Alabama at BirminghamCompleted
-
MelanomaPRO, RussiaRecruitingMelanoma | Melanoma (Skin) | Melanoma Stage IV | Melanoma Stage III | Melanoma, Stage II | Melanoma, Uveal | Melanoma in Situ | Melanoma, OcularRussian Federation
-
Diagram B.V.CompletedParoxysmal Atrial Fibrillation | Persistent Atrial Fibrillation | Out of Range Hypertension | Signs of Sympathetic OverdriveSpain, Netherlands
-
University of FloridaCompleted
-
University of California, Los AngelesCompleted