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The Nutritional Benefits of Metanx in Patients With Diabetic Peripheral Neuropathy (MEDIAN)

Not Applicable
Conditions
B Vitamin Deficiency
Diabetic Peripheral Neuropathy
Interventions
Other: Metanx
Other: Placebo
Registration Number
NCT01990092
Lead Sponsor
Pamlab, Inc.
Brief Summary

The objectives of the MEDIAN study are to evaluate the short-term and long-term safety and nutritional benefits of Metanx® versus placebo in subjects with mild to moderate diabetic peripheral neuropathy (DPN). Short-term effects will be evaluated during the first 16 weeks of treatment, and long-term effects will be evaluated over the duration of a 48 week treatment period.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
238
Inclusion Criteria
  • Be male or female between 25 and 80 years of age, inclusive, at the time of consent

  • Have a diagnosis of diabetes mellitus Type 2 as defined by the American Diabetes Association and on stable therapy as defined per the investigator's opinion for at least 1 month before the Screening Visit.

  • Have a diagnosis of DPN established at least 6 months but not greater than 7 years prior to Screening

  • If receiving DPN-related medication, doses must be stable for at least 6 weeks and should be taking only one of the following medications compliant with Exclusion Criterion 7:

    • Alpha-2-delta ligand [e.g., pregabalin (Lyrica) or gabapentin (Neurontin)
    • Anticonvulsant [e.g., carbamazepine, topiramate (Topamax), valproic acid (Depakote) or lamotrigine (Lamictal)]
    • Serotonin-norepinephrine Reuptake Inhibitor (SNRI) [e.g., duloxetine (Cymbalta) or venlafaxine (Effexor)]
    • Tricyclic antidepressant (TCA) [e.g., amitriptyline, nortriptyline, imipramine, and desipramine (Norpramin, Pertofrane)]
  • Have a score between 3 and 6, inclusive, on the Michigan Neuropathy Screening Instrument (MNSI) Part b

  • Have a minimum score of 6 on the NTSS-6 at Screening

  • Have negative urinalysis for drugs of abuse, such as amphetamines, barbiturates, cannabinoids, cocaine, or opiates

  • Have a negative urine pregnancy test at Screening if female and of childbearing potential

  • If female, must be either of nonchildbearing potential (surgically sterile or 2 years postmenopausal) or agree to use two methods of effective contraception such as hormonal contraception, intrauterine device or other mechanical contraception device, or condom plus spermicide during the subject's participation

  • If male, must be surgically sterile or agree to use two methods of effective contraception such as condom plus spermicide during the subject's participation

  • Have the ability to understand the requirements of the study, have provided written informed consent as evidenced by signature on an informed consent form (ICF) approved by an institutional review board (IRB), and agree to abide by the study restrictions and return to the site for the required assessments

  • Have provided written authorization for use and disclosure of protected health information

Exclusion Criteria
  • Be pregnant or lactating
  • Have a history of amputation, skin ulceration, and/or active Charcot of either foot
  • Have a history of previous surgery involving the spine or lower extremity, with residual symptoms of pain or difficulty with movement
  • Have Crohn's disease or a history of any type of bariatric surgery or any surgical resection of all or part of the stomach, duodenum, jejunum, and/or ileum. (Previous surgical resections of the colon that spared the stomach, duodenum, jejunum and ileum are allowed.)
  • Have a history of surgery or hospitalization within 2 months prior to Screening or planned hospitalization at any time during the study
  • Be taking systemic corticosteroids within 2 months prior to Screening, opiates or tramadol hydrochloride within 6 weeks prior to Screening, and/or immunosuppressives, or receiving radiotherapy within 6 months prior to Screening
  • Be taking more than one anticonvulsant, serotonin-norepinephrine reuptake inhibitor (SNRI), or tricyclic antidepressant (TCA)
  • Have ongoing evidence of peripheral vascular disease, including greater than one nonpalpable pulse on either foot, history of claudication, or history of lower extremity vascular bypass surgery or angioplasty
  • Have circulating glycated hemoglobin (HbA1c) exceeding 11% at Screening
  • Have an estimated glomerular filtration rate (eGFR) less than or equal to 40 ml/min using the Modification of Diet in Renal Disease (MDRD) formula at Screening or have end-stage renal disorder requiring hemodialysis
  • Have uncontrolled hypertension defined as sustained systolic blood pressure (SBP) greater than 200 mmHg or diastolic blood pressure (DBP) greater than 110 mmHg at screening
  • Have lung disease (uncontrolled asthma or shortness of breath) within 2 months prior to Screening
  • Use of any of the following supplements within 6 weeks before Screening: evening primrose oil, vitamin B12 injection, greater than 10 mg of vitamin B6, or greater than 800 µg of folate
  • Have previously failed two or more prior therapies for painful DPN
  • Currently abusing alcohol or drugs or have a history of such abuse within the past 3 years. (Alcohol abuse is defined as more than 2 drink units per day for women and more than 3 drink units per day for men. One drink unit is defined as 1.5 oz [45 mL] of distilled spirits, 5 oz [150 mL] of wine, or 12 oz [360 mL] of beer.)
  • Have any nondiabetic cause of peripheral neuropathy
  • Have a history of documented lumbar nerve entrapment or symptoms suggestive of a lumbar nerve entrapment
  • Have a history of systemic lupus erythematosis, rheumatoid arthritis, Sjögren's syndrome, or mixed connective tissue disease
  • If receiving thyroid replacement therapy, should be on a stable dose for at least 6 weeks prior to Screening
  • Have a history of a positive HIV test or active Hepatitis B or C infection.
  • Have a history or presence of malignancy within 10 years prior to Screening except for basal or squamous cell carcinoma of the skin. Records to be submitted to Pamlab for review and approval to randomize.
  • Have prior use of or intolerance to Metanx® or any of its active ingredients
  • Have been dosed or used a medical device in another investigational trial within 60 days prior to Screening.
  • Have any clinically significant existing medical, psychiatric, or nonmedical condition that in the opinion of the investigator places the subject at undue risk, prevents compliance with the study protocol, or potentially jeopardizes the quality of the data to be generated

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
MetanxMetanxSubjects will take 2 Metanx tablets once daily for 48 weeks.
PlaceboPlaceboSubjects will take 2 placebo tablets once daily for 48 weeks.
Primary Outcome Measures
NameTimeMethod
Change in plasma methylmalonic acid (MMA) levels16 weeks
Secondary Outcome Measures
NameTimeMethod
Change in neuropathic disability as measured by the Michigan Neuropathy Screening Instrument part B48 weeks

This neuropathy-specific measure will be evaluated to monitor for signs of disease progression.

Change in neuropathic symptoms as measured by the Neuropathy Total Symptom Score-6questionnaire(NTSS-6)16 weeks

This neuropathy-specific measure will be evaluated to monitor for signs of disease progression.

Change in neuropathic symptoms as measured by the Neuropathy Total Symptom Score-6 questionnaire (NTSS-6)48 weeks

This neuropathy-specific measure will be evaluated to monitor for signs of disease progression.

Change in plasma 5-methyltetrahydrofolate levels16 weeks
Change in plasma vitamin B6 levels16 weeks
Change in plasma vitamin B12 levels16 weeks
Change in urine microalbumin/creatinine ratio48 weeks
Change in epidermal nerve fiber density48 weeks

This neuropathy-specific measure will be evaluated to monitor for signs of disease progression.

Trial Locations

Locations (25)

Arizona Research Center

🇺🇸

Phoenix, Arizona, United States

Collaborative Neuroscience Network, LLC

🇺🇸

Long Beach, California, United States

Center for Clinical Research, Inc.

🇺🇸

San Francisco, California, United States

Meridien Research

🇺🇸

Bradenton, Florida, United States

PAB Clinical Research

🇺🇸

Brandon, Florida, United States

Suncoast Clinical Research, Inc.

🇺🇸

New Port Richey, Florida, United States

Suncoast Clinical Research

🇺🇸

Palm Harbor, Florida, United States

Florida Medical Clinic

🇺🇸

Wesley Chapel, Florida, United States

Renstar Medical Research

🇺🇸

Ocala, Florida, United States

North Chattahoochee Family Physicians, LLC

🇺🇸

Johns Creek, Georgia, United States

CRI Lifetree

🇺🇸

Philadelphia, Pennsylvania, United States

Urgent Care Specialists, LLC dba Hometown Urgent Care & Occupational Health

🇺🇸

Dayton, Ohio, United States

FutureSearch Trials of Neurology, L.P.

🇺🇸

Austin, Texas, United States

Centex Studies Inc.

🇺🇸

Houston, Texas, United States

Pioneer Research Solutions, Inc.

🇺🇸

Houston, Texas, United States

Northeast Clinical Research of San Anotnio, LLC

🇺🇸

Schertz, Texas, United States

ClinPoint Trials, LLC

🇺🇸

Waxahachie, Texas, United States

Strelitz Diabetes Center

🇺🇸

Norfolk, Virginia, United States

Coastal Connecticut Research, LLC

🇺🇸

New London, Connecticut, United States

Trinity Clinical Research, LLC

🇺🇸

Tullahoma, Tennessee, United States

Clinical Trials, Inc.

🇺🇸

Little Rock, Arkansas, United States

Willis-Knighton Physician Network / WKB Family Medicine Associates

🇺🇸

Bossier City, Louisiana, United States

Tulane University School of Medicine

🇺🇸

New Orleans, Louisiana, United States

Coastal Clinical Research, Inc.

🇺🇸

Mobile, Alabama, United States

Endeavor Clinical Trials, PA

🇺🇸

San Antonio, Texas, United States

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