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Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00679939
First received: May 15, 2008
Last updated: November 30, 2016
Last verified: November 2016
  Purpose
The purpose of this study is to determine the effects of rosiglitazone on the bone in postmenopausal women with type 2 diabetes mellitus

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: Rosiglitazone
Drug: Metformin
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A 52 Week Randomized, Double-Blind, Multicenter, Mechanistic Study With a 24 Week Open-Label Follow-Up to Evaluate the Effect of AVANDIA TM on Bone in Postmenopausal Women With Type 2 Diabetes Mellitus

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52 [ Time Frame: Baseline and Week 52 ]
    FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region. Change in FN BMD at Week 52 was only analyzed within the Rosiglitazone arm.

  • Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 76+10 Days [ Time Frame: Baseline and Week 76+10 days ]
    FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Baseline at Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) From Week 52 +10 Days to Week 76+10 Days [ Time Frame: Week 52+10 days and Week 76+10 days ]
    FN BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Bone mineral density is calculated as the mineral content of a bone divided by the area of the bone. DXA is the principal technique used for measuring BMD. Percent change from Week 52+10 days to Week 76+10 days was calculated as (BMD at Week 76+10 days minus BMD at Week 52+10 days)/BMD at Week 52+10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.


Secondary Outcome Measures:
  • Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52 [ Time Frame: Baseline and Week 52 ]
    BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Baseline at Week 52 was calculated as (BMD at Week 52 minus BMD at Baseline)/BMD at Baseline x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+10 Days to Week 76 + 10 Days [ Time Frame: Week 52 + 10 days and Week 76 + 10 days ]
    BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Week 52 + 10 days toat Week 76 + 10 days was calculated as (BMD at Week 76 + 10 days minus BMD at Week 52 + 10 days)/BMD at Week 52 + 10 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA From Week 52+30 Days to Week 76 + 30 Days [ Time Frame: Week 52 + 30 days and Week 76 + 30 days ]
    BMD (measured in grams per centimeters squared [g/cm^2]) was measured by DXA. Percent change from Week 52 + 30 days to Week 76 + 30 days was calculated as (BMD at Week 76 + 30 days minus BMD at Week 52 + 30 days)/BMD at Week 52 + 30 days x 100% and was assessed by analysis of covariance (ANCOVA) with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    BSAP and P1NP levels were measured in micrograms per liter (mcg/L) from blood samples. BSAP and P1NP are indicators of bone buildup or formation. GM, geometric mean; SE, standard error. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    CTX levels were measured in picograms per milliliter (pg/ml) from blood samples. CTX is an indicator of bone break down or resorption. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Vitamin D levels were measured in nanomoles per Liter (nmol/L) from blood samples. Vitamin D is required for good bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Intact PTH levels were measured in nanograms per Liter (ng/L) from blood samples. Intact PTH is the amount of PTH circulating in the blood and influences bone health. Percent change was based on log-transformed data and was assessed by an ANCOVA with terms for treatment, baseline value, prior therapy, and region.

  • Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data.

  • Percent Change in Serum Estradiol From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Serum estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Estradiol is one form of the female sex hormone estrogen and influences bone health. Percent change from baseline was based on log-transformed data.

  • Percent Change From Baseline in Total Testosterone at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data.

  • Percent Change in Total Testosterone From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Total testosterone levels were measured in nanomoles per Liter (nmol/L) from blood samples. Testosterone is a male sex hormone and influences bone health; total testosterone is the entire amount circulating in blood. Percent change from baseline was based on log-transformed data.

  • Percent Change From Baseline in Free Testosterone at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

  • Percent Change in Free Testosterone From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Free testosterone levels were measured as a percentage of total testosterone from blood samples. Free testosterone is the amount of testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

  • Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76 [ Time Frame: Baseline, Week 52, and Week 76 ]
    SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data.

  • Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    SHBG levels were measured in nanomoles per liter (nmol/L) from blood samples. SHBG binds to estradiol and testosterone and influences the amount of estradiol or testosterone available to the body for use. Percent change from baseline was based on log-transformed data.


Other Outcome Measures:
  • Percent Change in Percentage of Free Estradiol From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Free estradiol levels were measured as a percentage of serum estrogen from blood samples. Free estradiol is the amount of estrogen available to the body for use. Percent change was based on log-transformed data.

  • Percent Change in Free Estradiol From Week 52 to Week 76 [ Time Frame: Week 52 and Week 76 ]
    Free estradiol levels were measured in picomoles per Liter (pmol/L) from blood samples. Free estrodial is the amount of estrogen available to the body for use. Change was based on log-transformed data.


Enrollment: 226
Study Start Date: April 2008
Study Completion Date: September 2010
Primary Completion Date: September 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm 1 Treatment A
rosiglitazone up to 8mg/day
Drug: Rosiglitazone
up to 8mg/day
Active Comparator: Arm 2 Treatment B
metformin up to 2000mg/day
Drug: Metformin
up to 2000mg/day

  Eligibility

Ages Eligible for Study:   55 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Female, >55 to <80 years
  • >5 years menopausal
  • Type 2 Diabetes Mellitus (T2DM) diagnosis according to American Diabetes Association (ADA), American Association of Clinical Endocrinologists (AACE), Canadian Diabetes Association (CDA), World Health Organization/International Diabetes Federation (WHO/IDF)
  • Drug-naïve (HbA1c < or = 9.0%); OR Prior monotherapy, submaximal doses of metformin (< or = 1000mg Metformin), sulfonylureas (< or = 5mg Glyburide, < or = 10mg Glipizide or < or = 8mg glimepiride) or full dose Januvia (100mg) (HbA1c < or = 8.5%); OR Prior monotherapy, > submaximal doses of metformin (>1000mg) or sulfonylureas (>5mg Glyburide, >10mg Glipizide or >8mg glimepiride) (HbA1c < or = 7.0%)
  • Weighs <300 lbs (136.4 kg)
  • Two or more vertebra (L1-L4) suitable for BMD measurement by dual x-ray absorptiometry (DXA)
  • Absolute BMD value consistent with T-score >-2.5 at femoral neck, lumbar spine and total hip

Exclusion Criteria:

  • Type 1 Diabetes Mellitus (T1DM) or history of diabetic ketoacidosis (DKA)
  • Renal or hepatic disease (clinically significant)
  • Hepatocellular reaction, severe edema, or medically serious fluid event associated with thiazolidinedione (TZD)
  • Recent (<6mos) history or clinical intervention for angina or myocardial infarction or is taking nitrates
  • Any stage of heart failure, i.e. New York Heart Association (NYHA) class I-IV
  • Systolic BP >160mmHg or diastolic BP >90mmHg while on antihypertensive
  • Hypersensitivity to TZDs, biguanides
  • Prior treatment with two or more oral anti-diabetic (OAD) agents
  • Bilateral hip replacements
  • Concurrent diseases affecting bone metabolism
  • Active malabsorption syndrome
  • Serum calcium outside the central lab reference range
  • Thyroid replacement therapy, serum thyroid stimulating hormone (TSH) must be within range
  • Vitamin D deficiency
  • Previous treatment with: strontium, intravenous (IV) bisphosphonate, fluoride, hormones, calcineurin inhibitors or methotrexate
  • Chronic systemic corticosteroid [e.g. glucocorticoid, mineralocorticoid] treatment of no more than two intra-articular injections within the past year or use of oral parenteral, or long-term, high-dose inhaled corticosteroids
  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: NCT00679939

  Show 42 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Publications:
Study Data/Documents: Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: AVD111179
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00679939     History of Changes
Other Study ID Numbers: AVD111179 
Study First Received: May 15, 2008
Results First Received: January 7, 2011
Last Updated: November 30, 2016
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
Type 2 diabetes mellitus
bone
x-ray absorptiometry
bone biomarkers
dual-energy
bone mineral density

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Rosiglitazone
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 17, 2017