Clinical trial NCT00726713: 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
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetic Peripheral Neuropathy (DPN)
Keywords: Metanx
diabetes
neuropathy
folic acid
folate
L-methylfolate
vitamin B6
Pyridoxal 5'-phosphate
vitamin B12
methylcobalamin
Lead sponsor: Pamlab, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Tulane University Health Sciences Center
name: VA Nebraska Western Iowa Health Care System
name: Scott and White Hospital & Clinic
name: Dallas Diabetes and Endocrine Center
name: University of Alabama at Birmingham
name: dgd Research, Inc.
name: Baylor Health Care System
First posted: 2008-08-01
Enrollment: 214
Sex: ALL
Minimum age (years): 25
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks
timeFrame: VPT was measured a 0 (baseline), and 24 weeks
Secondary outcomes:
measure: Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6)
timeFrame: NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks
measure: Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24
timeFrame: NDS scores were taken at 0 (Baseline), 16, and 24 weeks
measure: Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24
timeFrame: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks
measure: Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24
timeFrame: SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks
measure: Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24
timeFrame: VAS scores were taken at 0 (Baseline) and 24 weeks
measure: (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24
timeFrame: Analyte levels were taken at 0 (Baseline) and 24 weeks
measure: (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24
timeFrame: HADS Scores scores were taken at 0 (Baseline) and 24 weeks
measure: Change From Baseline in Total Homocysteine at Week 16 and 24
timeFrame: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks
measure: (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24
timeFrame: Analyte levels were taken at 0 (Baseline) and 24 weeks
measure: (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24
timeFrame: Analyte levels were taken at 0 (Baseline) and 24 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham School of Medicine
state: Alabama
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center
state: Louisiana
city: Omaha
country: United States
facility: Omaha VA Medical Center
state: Nebraska
city: Dallas
country: United States
facility: Dallas Diabetes and Endocrine Center
state: Texas
city: San Antonio
country: United States
facility: dgd Research, Inc.
state: Texas
city: Temple
country: United States
facility: Scott and White Hospital & Clinic
state: Texas
Study officials:
affiliation: Tulane University Health Sciences Center
name: Vivian Fonseca, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.