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A One-year Randomized Controlled Trial Evaluating the Impact of Pioglitazone Versus Linagliptin on Bone Turnover Markers

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ClinicalTrials.gov Identifier: NCT02429232
Recruitment Status : Unknown
Verified October 2015 by National Taiwan University Hospital.
Recruitment status was:  Not yet recruiting
First Posted : April 29, 2015
Last Update Posted : October 27, 2015
Sponsor:
Information provided by (Responsible Party):
National Taiwan University Hospital

Brief Summary:

Diabetes mellitus is a common disease with much impact on human's health and is related to osteoporosis. But the mechanism remains unclear. The foreign researches revealed thiazolidinedione (TZD) would increase the risk of osteoporosis and bone fracture, specially elderly women. However, it is still controversial in terms of the youth and men. In Taiwan,there is few related study to analyze the relationship between TZD and steoporosis.

This is a multicenter randomized controlled study.


Condition or disease Intervention/treatment Phase
Osteoporosis Diabetes Mellitus Drug: Pioglitazone Drug: Linagliptin Phase 4

Detailed Description:

Diabetes mellitus is a common disease with much impact on human's health and is related to osteoporosis. But the mechanism remains unclear. The foreign researches revealed thiazolidinedione (TZD) would increase the risk of osteoporosis and bone fracture, especially elderly women. However, it is still controversial in terms of the youth and men. In Taiwan, there is few related study to analyze the relationship between TZD and osteoporosis.

This is a multicenter randomized controlled study.This study will recruit adult (age ³40 years) type 2 diabetes patients who is on metformin (³1500mg/day) currently with recent HbA1c between 7.0~8.5%.Patient who has history of macular edema, congestive heart failure (NYHA Fc III, IV), chronic renal failure (stage IV, V), AST or ALT above 2.5 times upper limit, Medical history of endocrinopathies, osteoporosis with bone fracture, cancer will be excluded. Current bone fracture undergoing treatment, pregnancy, breast feeder will also be excluded.

This is a 3-year project and will enroll 160 eligible volunteers who are to randomized into group A and B (80 in each). During the next 48 weeks group A and B will receive metformin+pioglitazone and metformin+linagliptin respectively. Blood sugar, renal, and liver functions will be examined every 12 weeks. Calcium, phosphorus, vitamin D level, and bone turnover markers (N-terminal propeptide of type 1 procollagen, bone-specific alkaline phosphatase, osteocalcin, serum C- telopeptide, type 5 tartrate resistant acid phosphatase (TRAP), pyridinoline and deoxypyridinoline crosslinks) will be checked each 6 months.

All the blood samples will be sent to one core laboratory center. The within-group differences will be examined by repeated-measure ANOVA. The between-group differences will be examined by Student's t test.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A One-year Randomized Controlled Trial Evaluating the Impact of Pioglitazone Versus Linagliptin on Bone Turnover Markers
Study Start Date : October 2015
Estimated Primary Completion Date : July 2017
Estimated Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Osteoporosis

Arm Intervention/treatment
Experimental: Pioglitazone
Pioglitazone 30 mg once daily will be administered orally for total 48 weeks.
Drug: Pioglitazone
Pioglitazone 30mg/tablet once daily
Other Name: Actos

Active Comparator: Linagliptin
Linagliptin 5 mg once daily will be administered orally for total 48 weeks.
Drug: Linagliptin
Linagliptin 5mg/tablet once daily
Other Name: Trajenta




Primary Outcome Measures :
  1. Change from baseline in bone turnover markers [ Time Frame: Screen, Week 24, 48 ]
    The primary objective is to assess the effect of TZD on skeleton as measured bone turnover markers over the 12 months treatment period.


Secondary Outcome Measures :
  1. Change from baseline in Estimated glomerular filtration rate( eGFR) [ Time Frame: Screen, Week 24, 48 ]
    The objective is to assess the effect of TZD on kidney by measurement of Estimated glomerular filtration rate( eGFR) over the 12 months treatment period.

  2. Change from baseline in renal function-serum Creatinine (Cr) level [ Time Frame: Screen, Week 24, 48 ]
    The secondary objective is to assess the effect of TZD on kidney by measurement of doubling time of serum Creatinine (Cr) level and urine biomarkers over the 12 months treatment period.

  3. Change from baseline in renal function-Urine Albumin-to-Creatinine Ratio(UACR) [ Time Frame: Screen, Week 24, 48 ]
    The secondary objective is to assess the effect of TZD on kidney by measurement of doubling time of Urine Albumin-to-Creatinine Ratio(UACR) and urine biomarkers over the 12 months treatment period.

  4. Change from baseline in urine biomarkers [ Time Frame: Screen, Week 24, 48 ]
    The secondary objective is to assess the effect of TZD on kidney by measurement of urine biomarkers over the 12 months treatment period.



Information from the National Library of Medicine

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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Males or females ≥ 40 years of age at Visit 1and females in postmenopause for one year
  • Documentation of type 2 diabetes mellitus as evidenced by one or more of the following criteria:

    1. With typical symptoms and random blood sugar ≥ 200 mg/dl
    2. 8-hour fasting blood sugar ≥ 126 mg/dl
    3. Oral glucose tolerance test ≥ 200 mg/dl
    4. HbA1c≥ 6.5%
  • Only receiving oral anti-diabetic drugs (excluding TZDs or DPP-4 inhibitors) till visit 1 at least 3 months, and the HbA1c is between 7.0~8.5 % in recent 3 months.
  • Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study.

Exclusion Criteria:

  • DM on oral anti-diabetic drugs less than 3 months.
  • Receiving treatment of TZDs or DPP-4 inhibitors prior to this study.
  • Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  • AST, ALT over 2.5 times of the upper limit.
  • Chronic kidney disease, stage 4 and 5.
  • Congestive heart failure, NYHA class III, IV
  • History of osteoporosis.
  • History of diseases known to affect bone metabolism:

Abnormal thyroid function or history of hyperthyroidism, Cushing's syndrome, hypogonadism, acromegaly, history of hypopituitarism or status post pituitary surgery and/or radiotherapy, hematopoietic disorders.

  • History of moderate to severe Diabetic macular edema (DME)
  • History of moderate to severe diabetic retinopathy.
  • History of fracture over lumbar spine or hip joint or femoral head or forearm or any site of bone fracture undergoes treatment currently.
  • Who had taken any of the following medications prior to screening:

Corticosteroid, heparin, anticonvulsants, aluminum-containing antacid, proton pump inhibitor, immunosuppressant user within 3 months. Bisphosphonate, systemic fluoride treatment, PHT analogue, calcitonin, Denosumab, Strontium ranelate, hormone replacement therapy (androgen/estrogen/progesterone, thyroxine, growth hormone), selective estrogen receptor modulator /SERM (Tamoxifene, Raloxifene), selective tissue estrogenic activity regulator /STEAR (Tibolone), aromatase inhibitors within 1 year.

  • History of cancer.
  • Bed-ridden patients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02429232


Contacts
Contact: Feng-Jung Nien, MD 886-2-23123456 ext 66046 fj.nien@gmail.com
Contact: Chin-Hsiao Tseng, MD, PhD 886-2-23123456 ext 67247 ccktsh@ms6.hinet.net

Sponsors and Collaborators
National Taiwan University Hospital
Investigators
Principal Investigator: Chin-Hsiao Tseng, MD, PhD Department of Medicine,National Taiwan University Hospital

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT02429232     History of Changes
Other Study ID Numbers: 201312136MIND
First Posted: April 29, 2015    Key Record Dates
Last Update Posted: October 27, 2015
Last Verified: October 2015

Keywords provided by National Taiwan University Hospital:
Pioglitazone
Linagliptin
Diabetes mellitus
Diabetic macular edema
Kidney

Additional relevant MeSH terms:
Diabetes Mellitus
Osteoporosis
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Pioglitazone
Linagliptin
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action