Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN)

This study has been completed.
Sponsor:
Collaborators:
Tulane University Health Sciences Center
Omaha VA Medical Center
Scott and White Hospital & Clinic
Dallas Diabetes and Endocrine Center
University of Alabama at Birmingham
dgd Research, Inc.
Baylor Health Care System
Information provided by (Responsible Party):
Pamlab, Inc.
ClinicalTrials.gov Identifier:
NCT00726713
First received: July 30, 2008
Last updated: July 26, 2013
Last verified: July 2013
  Purpose

The purpose of this research study is to determine if Metanx improves sensory neuropathy in persons with Type 2 diabetes. Metanx is a medical food available with a prescription from a physician. It consists of L-methylfolate, Pyridoxal 5'-phosphate, and Methylcobalamin, which are the active forms of folate, vitamin B6, and vitamin B12, respectively. Subjects will be randomly assigned to receive either Metanx or placebo for 6 months.


Condition Intervention Phase
Type 2 Diabetic Peripheral Neuropathy (DPN)
Other: Metanx (a medical food)
Other: Metanx placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A 24 Week, Double-blind, Placebo-controlled, Multisite Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN)

Resource links provided by NLM:


Further study details as provided by Pamlab, Inc.:

Primary Outcome Measures:
  • Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks [ Time Frame: VPT was measured a 0 (baseline), and 24 weeks ] [ Designated as safety issue: No ]
    Vibration Perception Threshold (VPT) 25-45 volts at hallux on either leg as measured by VPT meter on the great toe of each foot. Mean VPT averaged across both toes.


Secondary Outcome Measures:
  • Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) [ Time Frame: NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks ] [ Designated as safety issue: No ]

    This measure was taken to determine if Metanx® (compared to placebo) changes neuropathic symptoms as evaluated by the Neuropathy Total Symptom Score-6 (NTSS-6)

    The Neuropathy Total Symptom Score-6 Scale (NTSS-6) is a validated scale that evaluates individual neuropathy sensory symptoms in patients with diabetes mellitus (DM) and diabetic peripheral neuropathy (DPN). This scale was a modified 6 item scale that consists of yes or no questions. Scores range between 0 and 21.96, a higher score indicates greater severity of symptoms. After adjusting for baseline measurements scores are reflected as negative numbers. Negative numbers indicate improvement in symptoms. ie. a change from baseline after 24 weeks of -2 would be a greater improvement than a change in baseline of -1 after 24 weeks.


  • Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 [ Time Frame: NDS scores were taken at 0 (Baseline), 16, and 24 weeks ] [ Designated as safety issue: No ]

    This outcome was taken to determine if Metanx® (compared to placebo) has an effect on clinical examination as determined by the Neuropathy Disability Score (NDS)

    The Neuropathy Disability Score (NDS) evaluates the severity of individual symptoms of neuropathy. A simple visual numeric distress scale is used that ranges from 0 to 10. The most favorable score is 0, which indicates an absence of symptoms. The most severe symptoms possible would be recorded as a score of 10.


  • Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 [ Time Frame: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks ] [ Designated as safety issue: No ]
    To determine if Metanx® (compared to placebo) affects a change in subject's total folate and total methyl malonic acid (MMA) at week 16 and 24

  • Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 [ Time Frame: SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks ] [ Designated as safety issue: No ]

    To determine if Metanx® (compared to placebo) affects a subject's "quality of life" as determined by the SF-36 questionnaire

    The Short Form- 36 Mental Component Summary (SF-36 MCS) and SF-36 Physical Component Summary (SF-36 PCS) both measure health related quality of life, the MCS quantifying mental health and the PCS quantifying physical function. They are both scored on 100 point scales with 0 representing the worst possible outcome and 100 representing the most optimal possible scoring


  • Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 [ Time Frame: VAS scores were taken at 0 (Baseline) and 24 weeks ] [ Designated as safety issue: No ]

    To determine if Metanx® (compared to placebo) affects a subject's lower extremity pain level using a 10-point Visual Analog Scale at Baseline and 24-week evaluation visits.

    The Visual Analog Scale (VAS) measures a patients sensation of pain. A 10-cm visual analog scale is used. A measurement on the 10 cm analog scale is used to quantify the level of pain indicated with 0 cm indicating "no pain" and 10 cm indicating the "worst pain imaginable".


  • (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 [ Time Frame: Analyte levels were taken at 0 (Baseline) and 24 weeks ] [ Designated as safety issue: No ]
    (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory marker levels, including IL-6 and TNF-α

  • (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 [ Time Frame: HADS Scores scores were taken at 0 (Baseline) and 24 weeks ] [ Designated as safety issue: No ]
    The Hospital Anxiety and Depression Scale (HADS) consists of a 14-item questionnaire that provides a measurement of depression. Each item is rated on a 4-point scale, giving a maximum scores of 21 for the most severe depression. Depression was evaluated using the Hospital Anxiety and Depression Scale (HADS) question inventory at Baseline, and 24-week evaluation visits

  • Change From Baseline in Total Homocysteine at Week 16 and 24 [ Time Frame: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks ] [ Designated as safety issue: No ]
    To determine if Metanx® (compared to placebo) affects change in subjects total homocysteine levels

  • (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 [ Time Frame: Analyte levels were taken at 0 (Baseline) and 24 weeks ] [ Designated as safety issue: No ]
    (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including hs-CRP

  • (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 [ Time Frame: Analyte levels were taken at 0 (Baseline) and 24 weeks ] [ Designated as safety issue: No ]
    (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including Potential Antioxidant (PAO)


Enrollment: 214
Study Start Date: June 2008
Study Completion Date: June 2011
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Metanx
Other: Metanx (a medical food)
Metanx one tablet twice a day
Placebo Comparator: 2
Placebo
Other: Metanx placebo
Metanx placebo one tablet twice a day

  Eligibility

Ages Eligible for Study:   25 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female between 25 and 80 years of age (inclusive);
  2. Documented diabetes mellitus Type 2 (Based upon ADA criteria);
  3. Peripheral polyneuropathy: Vibration Perception Threshold (VPT) 25-45 Volts at hallux on either leg.
  4. Adequate lower extremity vascular status:

    • Palpable pedal pulse in both feet;
    • No intermittent claudication;
    • No history of lower extremity vascular bypass surgery or angioplasty
  5. The subject is able to understand the information in the informed consent form and is willing and able to sign the consent.

Exclusion Criteria:

  1. Amputation of any kind or an ulceration within the last two (2) years including at Screen;
  2. History or active Charcot neuroarthropathy on either foot;
  3. Previous surgery to spine or lower extremity with residual symptoms of pain or difficulty with movement;
  4. Severe rheumatoid arthritis or osteoarthritis that would cause discomfort during causal walking or stair climbing;
  5. Current treatment with systemic steroids, immunosuppressives, or radiotherapy;
  6. Peripheral vascular disease defined as any nonpalpable foot pulse, history of claudication, or a history of lower extremity vascular bypass surgery or angioplasty;
  7. Glycated hemoglobin (HbA1c) >9 at Screen.
  8. Uncontrolled heart (Hypertension: BP > 160/90), or lung disease (uncontrolled asthma or shortness of breath) in the last 2 months prior to Screen;
  9. End stage kidney disorder requiring hemodialysis or serum creatinine > 2.5X (normal upper limit);
  10. The following supplements within 2 months prior to Screen: alpha lipoic acid; B12 injection; >10mg of B6; or, > 800mcg of folate;
  11. Taking either an opiate at any dose or on the maximum dose of any anticonvulsant;
  12. Pregnant or nursing;
  13. Life expectancy < 12 months;
  14. Initiated therapies for Painful Diabetic Neuropathy (pregabalin, gabapentin, duloxetine etc.) in the last 2 months prior to Screen;
  15. Initiated new hyperglycemic, insulin, statin or hypertensive therapies within 2 months prior to Screen (dose modifications of current therapies are allowed at the discretion of the investigator);
  16. Current alcohol or drug abuse (or history of such abuse within the past 3 years); and,
  17. Not willing or able to follow procedures specified by the protocol and/or the instructions of the study personnel.
  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: NCT00726713

Locations
United States, Alabama
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, United States, 35294
United States, Louisiana
Tulane University Health Sciences Center
New Orleans, Louisiana, United States, 70112
United States, Nebraska
Omaha VA Medical Center
Omaha, Nebraska, United States, 68105
United States, Texas
Dallas Diabetes and Endocrine Center
Dallas, Texas, United States, 75230
dgd Research, Inc.
San Antonio, Texas, United States, 78229
Scott and White Hospital & Clinic
Temple, Texas, United States, 76504
Sponsors and Collaborators
Pamlab, Inc.
Tulane University Health Sciences Center
Omaha VA Medical Center
Scott and White Hospital & Clinic
Dallas Diabetes and Endocrine Center
University of Alabama at Birmingham
dgd Research, Inc.
Baylor Health Care System
Investigators
Principal Investigator: Vivian Fonseca, MD Tulane University Health Sciences Center
  More Information

Publications:
Responsible Party: Pamlab, Inc.
ClinicalTrials.gov Identifier: NCT00726713     History of Changes
Other Study ID Numbers: M-001
Study First Received: July 30, 2008
Results First Received: May 2, 2013
Last Updated: July 26, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Pamlab, Inc.:
Metanx
diabetes
neuropathy
folic acid
folate
L-methylfolate
vitamin B6
Pyridoxal 5'-phosphate
vitamin B12
methylcobalamin

Additional relevant MeSH terms:
Peripheral Nervous System Diseases
Diabetic Neuropathies
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases

ClinicalTrials.gov processed this record on September 18, 2014