Clinical trial NCT00679939: Study In Postmenopausal Women With Type 2 Diabetes Looking At Approved Diabetes Drugs And How They Affect Bone Health
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 2
Keywords: Type 2 diabetes mellitus
bone
x-ray absorptiometry
bone biomarkers
dual-energy
bone mineral density
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2008-05-19
Enrollment: 226
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effects of rosiglitazone on the bone in postmenopausal women with type 2 diabetes mellitus


Eligibility 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

Primary outcomes:
measure: Adjusted Percent Change From Baseline in Femoral Neck (FN) Bone Mineral Density (BMD) Via Dual-energy X-ray Absorptiometry (DXA) at Week 52
timeFrame: Baseline and Week 52
measure: 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
timeFrame: Baseline and Week 76+10 days
measure: 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
timeFrame: Week 52+10 days and Week 76+10 days
Secondary outcomes:
measure: Adjusted Percent Change From Baseline in Femoral Neck, Total Hip, Trochanter, and Lumbar Spine BMD Via DXA at Week 52
timeFrame: Baseline and Week 52
measure: 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
timeFrame: Week 52 + 10 days and Week 76 + 10 days
measure: 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
timeFrame: Week 52 + 30 days and Week 76 + 30 days
measure: Adjusted Percent Change From Baseline in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Adjusted Percent Change in Bone Specific Alkaline Phosphatase (BSAP) and Procollagen Type 1 N-propeptide (P1NP) From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Adjusted Percent Change From Baseline in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Adjusted Percent Change in Carboxyterminal Cross-linked Telopeptide of Type 1 Collagen (CTX) From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Adjusted Percent Change From Baseline in 25-Hydroxyvitamin D (Vitamin D) at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Adjusted Percent Change in 25-Hydroxyvitamin D (Vitamin D) From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Adjusted Percent Change From Baseline in Intact Parathyroid Hormone (PTH) at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Adjusted Percent Change in Intact Parathyroid Hormone (PTH) From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Percent Change From Baseline in Serum Estradiol at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Percent Change in Serum Estradiol From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Percent Change From Baseline in Total Testosterone at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Percent Change in Total Testosterone From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Percent Change From Baseline in Free Testosterone at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Percent Change in Free Testosterone From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Percent Change From Baseline in Sex Hormone Binding Globulin (SHBG) at Week 52 and Week 76
timeFrame: Baseline, Week 52, and Week 76
measure: Percent Change in Sex Hormone Binding Globulin (SHBG) From Week 52 to Week 76
timeFrame: Week 52 and Week 76
Other outcomes:
measure: Percent Change in Percentage of Free Estradiol From Week 52 to Week 76
timeFrame: Week 52 and Week 76
measure: Percent Change in Free Estradiol From Week 52 to Week 76
timeFrame: Week 52 and Week 76
Locations:
city: Tucson
country: United States
facility: GSK Investigational Site
state: Arizona
city: Huntington Park
country: United States
facility: GSK Investigational Site
state: California
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Sacramento
country: United States
facility: GSK Investigational Site
state: California
city: San Diego
country: United States
facility: GSK Investigational Site
state: California
city: Torrance
country: United States
facility: GSK Investigational Site
state: California
city: Vista
country: United States
facility: GSK Investigational Site
state: California
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Lexington
country: United States
facility: GSK Investigational Site
state: Kentucky
city: Slidell
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Las Vegas
country: United States
facility: GSK Investigational Site
state: Nevada
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: Albuquerque
country: United States
facility: GSK Investigational Site
state: New Mexico
city: East Syracuse
country: United States
facility: GSK Investigational Site
state: New York
city: Kingston
country: United States
facility: GSK Investigational Site
state: New York
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Columbia
country: United States
facility: GSK Investigational Site
state: South Carolina
city: Kingsport
country: United States
facility: GSK Investigational Site
state: Tennessee
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Wenatchee
country: United States
facility: GSK Investigational Site
state: Washington
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Brampton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Granby
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Tallinn
country: Estonia
facility: GSK Investigational Site
city: Tallin
country: Estonia
facility: GSK Investigational Site
city: Cuernavaca
country: Mexico
facility: GSK Investigational Site
state: Morelos
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Mérida
country: Mexico
facility: GSK Investigational Site
state: Yucatán
city: Durango
country: Mexico
facility: GSK Investigational Site
city: Lahore
country: Pakistan
facility: GSK Investigational Site
city: Manila
country: Philippines
facility: GSK Investigational Site
city: Marikina City
country: Philippines
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Benidorm/Alicante
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Granada
country: Spain
facility: GSK Investigational Site
city: Petrer
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Fitzpatrick LA, Bilezikian JP, Wooddell M, Paul G, Kolatkar NS, Nino AJ, Miller CG, Bogado CE, Arnaud CD, Cobitz AR. Mechanism of action study to evaluate the effect of rosiglitazone on bone in postmenopausal women with type 2 diabetes mellitus: rationale, study design and baseline characteristics. J Drug Assess. 2011 Dec 16;1(1):11-9. doi: 10.3109/21556660.2011.641703. eCollection 2012.
citation: Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.
citation: Miller CG, Bogado CC, Nino AJ, Northcutt AR, Yu HJ, Lewiecki EM, Paul G, Cobitz AR, Wooddell MJ, Bilezikian JP, Fitzpatrick LA. Evaluation of Quantitative Computed Tomography Cortical Hip Quadrant in a Clinical Trial With Rosiglitazone: A Potential New Study Endpoint. J Clin Densitom. 2016 Oct;19(4):485-491. doi: 10.1016/j.jocd.2016.02.003. Epub 2016 Mar 24.
citation: Bilezikian JP, Josse RG, Eastell R, Lewiecki EM, Miller CG, Wooddell M, Northcutt AR, Kravitz BG, Paul G, Cobitz AR, Nino AJ, Fitzpatrick LA. Rosiglitazone decreases bone mineral density and increases bone turnover in postmenopausal women with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2013 Apr;98(4):1519-28. doi: 10.1210/jc.2012-4018. Epub 2013 Feb 28.