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

Primary Purpose

Osteoporosis, Diabetes Mellitus

Status

Unknown status

Phase

Phase 4

Locations

Study Type

Interventional

Intervention

Pioglitazone

Linagliptin

About this trial

This is an interventional treatment trial for Osteoporosis focused on measuring Pioglitazone, Linagliptin, Diabetes mellitus, Diabetic macular edema, Kidney

Eligibility Criteria

40 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Pioglitazone

Linagliptin

Arm Description

Pioglitazone 30 mg once daily will be administered orally for total 48 weeks.

Linagliptin 5 mg once daily will be administered orally for total 48 weeks.

Outcomes

Primary Outcome Measures

Change from baseline in bone turnover markers

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

Change from baseline in Estimated glomerular filtration rate( eGFR)

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.

Change from baseline in renal function-serum Creatinine (Cr) level

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.

Change from baseline in renal function-Urine Albumin-to-Creatinine Ratio(UACR)

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.

Change from baseline in urine biomarkers

The secondary objective is to assess the effect of TZD on kidney by measurement of urine biomarkers over the 12 months treatment period.

Full Information

NCT ID

NCT02429232

First Posted

April 7, 2015

Last Updated

October 25, 2015

Sponsor

National Taiwan University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT02429232

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Unknown status

Study Start Date

October 2015 (undefined)

Primary Completion Date

July 2017 (Anticipated)

Study Completion Date

December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

National Taiwan University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Osteoporosis, Diabetes Mellitus

Keywords

Pioglitazone, Linagliptin, Diabetes mellitus, Diabetic macular edema, Kidney

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Pioglitazone

Arm Type

Experimental

Arm Description

Pioglitazone 30 mg once daily will be administered orally for total 48 weeks.

Arm Title

Linagliptin

Arm Type

Active Comparator

Arm Description

Linagliptin 5 mg once daily will be administered orally for total 48 weeks.

Intervention Type

Drug

Intervention Name(s)

Pioglitazone

Other Intervention Name(s)

Actos

Intervention Description

Pioglitazone 30mg/tablet once daily

Intervention Type

Drug

Intervention Name(s)

Linagliptin

Other Intervention Name(s)

Trajenta

Intervention Description

Linagliptin 5mg/tablet once daily

Primary Outcome Measure Information:

Title

Change from baseline in bone turnover markers

Description

The primary objective is to assess the effect of TZD on skeleton as measured bone turnover markers over the 12 months treatment period.

Time Frame

Screen, Week 24, 48

Secondary Outcome Measure Information:

Title

Change from baseline in Estimated glomerular filtration rate( eGFR)

Description

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.

Time Frame

Screen, Week 24, 48

Title

Change from baseline in renal function-serum Creatinine (Cr) level

Description

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.

Time Frame

Screen, Week 24, 48

Title

Change from baseline in renal function-Urine Albumin-to-Creatinine Ratio(UACR)

Description

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.

Time Frame

Screen, Week 24, 48

Title

Change from baseline in urine biomarkers

Description

The secondary objective is to assess the effect of TZD on kidney by measurement of urine biomarkers over the 12 months treatment period.

Time Frame

Screen, Week 24, 48

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Accepts Healthy Volunteers

Eligibility 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: With typical symptoms and random blood sugar ≥ 200 mg/dl 8-hour fasting blood sugar ≥ 126 mg/dl Oral glucose tolerance test ≥ 200 mg/dl 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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Feng-Jung Nien, MD

Phone

886-2-23123456

Ext

66046

fj.nien@gmail.com

First Name & Middle Initial & Last Name or Official Title & Degree

Chin-Hsiao Tseng, MD, PhD

Phone

886-2-23123456

Ext

67247

ccktsh@ms6.hinet.net

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chin-Hsiao Tseng, MD, PhD

Organizational Affiliation

Department of Medicine,National Taiwan University Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

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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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