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

Primary Purpose

Type 2 Diabetic Peripheral Neuropathy (DPN)

Status

Completed

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Metanx (a medical food)

Metanx placebo

About this trial

This is an interventional treatment trial for Type 2 Diabetic Peripheral Neuropathy (DPN) focused on measuring Metanx, diabetes, neuropathy, folic acid, folate, L-methylfolate, vitamin B6, Pyridoxal 5'-phosphate, vitamin B12, methylcobalamin

Eligibility Criteria

25 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Male or female between 25 and 80 years of age (inclusive);
Documented diabetes mellitus Type 2 (Based upon ADA criteria);
Peripheral polyneuropathy: Vibration Perception Threshold (VPT) 25-45 Volts at hallux on either leg.
Adequate lower extremity vascular status:
- Palpable pedal pulse in both feet;
- No intermittent claudication;
- No history of lower extremity vascular bypass surgery or angioplasty
The subject is able to understand the information in the informed consent form and is willing and able to sign the consent.

Exclusion Criteria:

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

Sites / Locations

University of Alabama at Birmingham School of Medicine
Tulane University Health Sciences Center
Omaha VA Medical Center
Dallas Diabetes and Endocrine Center
dgd Research, Inc.
Scott and White Hospital & Clinic

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Arm Description

Metanx

Placebo

Outcomes

Primary Outcome Measures

Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks

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)

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

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

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

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

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

(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

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

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

(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

(Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including Potential Antioxidant (PAO)

Full Information

NCT ID

NCT00726713

First Posted

July 30, 2008

Last Updated

July 26, 2013

Sponsor

Pamlab, Inc.

Collaborators

Tulane University Health Sciences Center, VA Nebraska Western Iowa Health Care System, Scott and White Hospital & Clinic, Dallas Diabetes and Endocrine Center, University of Alabama at Birmingham, dgd Research, Inc., Baylor Health Care System

1. Study Identification

Unique Protocol Identification Number

NCT00726713

Brief Title

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

Official Title

A 24 Week, Double-blind, Placebo-controlled, Multisite Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN)

Study Type

Interventional

2. Study Status

Record Verification Date

July 2013

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

May 2010 (Actual)

Study Completion Date

June 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Pamlab, Inc.

Collaborators

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

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

Type 2 Diabetic Peripheral Neuropathy (DPN)

Keywords

Metanx, diabetes, neuropathy, folic acid, folate, L-methylfolate, vitamin B6, Pyridoxal 5'-phosphate, vitamin B12, methylcobalamin

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

214 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Experimental

Arm Description

Metanx

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Other

Intervention Name(s)

Metanx (a medical food)

Intervention Description

Metanx one tablet twice a day

Intervention Type

Other

Intervention Name(s)

Metanx placebo

Intervention Description

Metanx placebo one tablet twice a day

Primary Outcome Measure Information:

Title

Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks

Description

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.

Time Frame

VPT was measured a 0 (baseline), and 24 weeks

Secondary Outcome Measure Information:

Title

Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6)

Description

Time Frame

NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks

Title

Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24

Description

Time Frame

NDS scores were taken at 0 (Baseline), 16, and 24 weeks

Title

Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24

Description

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

Time Frame

Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks

Title

Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24

Description

Time Frame

SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks

Title

Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24

Description

Time Frame

VAS scores were taken at 0 (Baseline) and 24 weeks

Title

(Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24

Description

(Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory marker levels, including IL-6 and TNF-α

Time Frame

Analyte levels were taken at 0 (Baseline) and 24 weeks

Title

(Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24

Description

Time Frame

HADS Scores scores were taken at 0 (Baseline) and 24 weeks

Title

Change From Baseline in Total Homocysteine at Week 16 and 24

Description

To determine if Metanx® (compared to placebo) affects change in subjects total homocysteine levels

Time Frame

Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks

Title

(Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24

Description

(Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including hs-CRP

Time Frame

Analyte levels were taken at 0 (Baseline) and 24 weeks

Title

(Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24

Description

(Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including Potential Antioxidant (PAO)

Time Frame

Analyte levels were taken at 0 (Baseline) and 24 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

25 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Male or female between 25 and 80 years of age (inclusive); Documented diabetes mellitus Type 2 (Based upon ADA criteria); Peripheral polyneuropathy: Vibration Perception Threshold (VPT) 25-45 Volts at hallux on either leg. Adequate lower extremity vascular status: Palpable pedal pulse in both feet; No intermittent claudication; No history of lower extremity vascular bypass surgery or angioplasty The subject is able to understand the information in the informed consent form and is willing and able to sign the consent. Exclusion Criteria: Amputation of any kind or an ulceration within the last two (2) years including at Screen; History or active Charcot neuroarthropathy on either foot; Previous surgery to spine or lower extremity with residual symptoms of pain or difficulty with movement; Severe rheumatoid arthritis or osteoarthritis that would cause discomfort during causal walking or stair climbing; Current treatment with systemic steroids, immunosuppressives, or radiotherapy; Peripheral vascular disease defined as any nonpalpable foot pulse, history of claudication, or a history of lower extremity vascular bypass surgery or angioplasty; Glycated hemoglobin (HbA1c) >9 at Screen. Uncontrolled heart (Hypertension: BP > 160/90), or lung disease (uncontrolled asthma or shortness of breath) in the last 2 months prior to Screen; End stage kidney disorder requiring hemodialysis or serum creatinine > 2.5X (normal upper limit); The following supplements within 2 months prior to Screen: alpha lipoic acid; B12 injection; >10mg of B6; or, > 800mcg of folate; Taking either an opiate at any dose or on the maximum dose of any anticonvulsant; Pregnant or nursing; Life expectancy < 12 months; Initiated therapies for Painful Diabetic Neuropathy (pregabalin, gabapentin, duloxetine etc.) in the last 2 months prior to Screen; 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); Current alcohol or drug abuse (or history of such abuse within the past 3 years); and, Not willing or able to follow procedures specified by the protocol and/or the instructions of the study personnel.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vivian Fonseca, MD

Organizational Affiliation

Tulane University Health Sciences Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Alabama at Birmingham School of Medicine

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35294

Country

United States

Facility Name

Tulane University Health Sciences Center

City

New Orleans

State/Province

Louisiana

ZIP/Postal Code

70112

Country

United States

Facility Name

Omaha VA Medical Center

City

Omaha

State/Province

Nebraska

ZIP/Postal Code

68105

Country

United States

Facility Name

Dallas Diabetes and Endocrine Center

City

Dallas

State/Province

Texas

ZIP/Postal Code

75230

Country

United States

Facility Name

dgd Research, Inc.

City

San Antonio

State/Province

Texas

ZIP/Postal Code

78229

Country

United States

Facility Name

Scott and White Hospital & Clinic

City

Temple

State/Province

Texas

ZIP/Postal Code

76504

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

23218892

Citation

Fonseca VA, Lavery LA, Thethi TK, Daoud Y, DeSouza C, Ovalle F, Denham DS, Bottiglieri T, Sheehan P, Rosenstock J. Metanx in type 2 diabetes with peripheral neuropathy: a randomized trial. Am J Med. 2013 Feb;126(2):141-9. doi: 10.1016/j.amjmed.2012.06.022. Epub 2012 Dec 5.

Results Reference

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

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