Advanced Glycation Endproducts and Bone Material Strength in T2D Treated With Pyridoxamine

Advanced Glycation Endproducts and Bone Material Strength in Type 2 Diabetes Treated With Pyridoxamine

The purpose of this study is to determine if a specific form of Vitamin B known as Pyridoxamine helps improve bone strength over one year in women (>65 yrs old) with Type 2 Diabetes. The investigators know that people with type 2 diabetes have the lower bone material strength and the investigators suspect this is due to high levels of circulating sugars that build up over time (known as Advanced Glycation Endproducts). The investigators will study whether using a specific form of vitamin B, known as pyridoxamine helps improve bone strength and reduce levels of circulating sugars over a one year time period.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: placebo; Dietary supplement: Pyridoxamine Dihydrochloride

Detailed Description

Type 2 Diabetes Mellitus (T2DM) has become one of the most important diseases of our time. Recent research shows that diabetes has negative effects on bones and that people with diabetes might more likely to break a bone. The investigators don't know the reasons for this, but the investigators suspect that normal bone replacement is slowed down in diabetes and this could slow down the growth of new bone. It is possible that the normal material becomes weaker because sugar-related components ("Advanced Glycation Endproducts") are making the bone more brittle. The investigators have shown in past research that people who have type 2 diabetes are more likely to have both weaker bone with lower "bone material strength" and also higher level of sugar-related components("Advanced Glycation Endproducts"). This study will focus on attempting to lower the sugar-related components("Advanced Glycation Endproducts") by treating a group of patients with type 2 diabetes with an over- the- counter B vitamin, known as vitamin B6 or pyridoxamine for one year. The investigators will compare post-menopausal women both before and after pyridoxamine use and study them in terms of different bone features based on blood tests, bone imaging, a bone indentation test and a measurement of sugar-related components in the skin. This study will help to clarify if using pyridoxamine helps improve bone strength in women with diabetes.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center - Harkness Pavillion

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women ≥65 years
• Diagnosis of T2D for ≥ 5 years, with all HbA1c levels.

Exclusion Criteria:

• Hormone replacement treatment (HTR) use (to avoid the influence of estrogen).
• Fractures (excluding skull, facial bones, metacarpals, fingers, toes, and fractures associated with severe trauma) within 12 months.
• A history of pathological fractures (eg, due to Paget's disease, myeloma, metastatic malignancy).
• Type 1 diabetes
• Disorders associated with altered skeletal structure or function (chronic liver disease' chronic renal disease stage 4 [eGFR < 30 mL/mim/1.73 m2] or worse, malignancy, hypoparathyroidism or hyperparathyroidism,acromegaly, Cushing's syndrome, hypopituitarism, alcohol intake > 3U/day).
• Treatment with any of the following drugs in part year:current corticosteroid, anticonvulsant therapy(phenytoin, phenobarbital, primidone, carbamazepine), SGLT2 inhibitor if on it for < 1 year), pharmacological doses of thyroid hormone (TSH<normal), adrenal or anabolic steroids, Aromatase inhibitors, calcitonin, bisphosphonates, denosumab, estrogen, or selective estrogen receptor modulator, sodium fluoride, teriparatide, thiazolidinediones(TZDs).
• Serum 25(OH)D levels < 20 ng/ml. If 25(OH)D levels are < 20 ng/ml, rescreening will be allowed following a vitamin D loading regimen of 50,000 IU/week for 4 weeks. If serum 25(OH) D levels are ≥ 20 ng/ml after supplementation, the subject will be allowed to enroll.
• Current use of pyridoxamine (although not multivitamin or vitamin B6 users because pyridoxamine is not at pharmacologic levels in these supplements).
• Allergy to pyridoxamine and vitamin B6.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: pyridoxamine; pyridoxamine dihydrochloride (over- the- counter type of vitamin B6) 200 mg po bid for one year	Dietary supplement: Pyridoxamine Dihydrochloride; pyridoxamine dihydrochloride (over- the- counter type of vitamin B6) 200 mg po bid
Placebo Comparator: identical placebo; identical placebo po bid for one year	Drug: placebo; placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone formation in serum by P1NP	change in serum biochemical marker of bone formation, P1NP	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Advanced glycation endproducts	Skin assessment of advanced glycation endproducts	12 months

Collaborators and Investigators

• Sponsor: Columbia University
• Investigators: Principal Investigator: Mishaela Rubin,, M.D, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2018
• Primary Completion (Actual): February 28, 2022
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: December 12, 2018
• First Submitted That Met QC Criteria: December 17, 2018
• First Posted (Actual): December 19, 2018

Study Record Updates

• Last Update Posted (Actual): August 3, 2022
• Last Update Submitted That Met QC Criteria: August 1, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes; Vitamin B6
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Pyridoxamine
• Other Study ID Numbers: AAAR5451

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No