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

Sponsor

Pamlab, Inc. (Industry)

Overall Status

Unknown status

CT.gov ID

NCT01990092

Collaborator

(none)

238

Enrollment

Locations

Arms

51.9

Duration (Months)

9.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetic Peripheral Neuropathy B Vitamin Deficiency	Other: Metanx Other: Placebo	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

238 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety and Nutritional Benefits of Metanx® in Subjects With Diabetic Peripheral Neuropathy

Study Start Date :

Nov 1, 2013

Anticipated Primary Completion Date :

Aug 1, 2016

Anticipated Study Completion Date :

Mar 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metanx Subjects will take 2 Metanx tablets once daily for 48 weeks.	Other: Metanx Metanx is a prescription medical food.
Placebo Comparator: Placebo Subjects will take 2 placebo tablets once daily for 48 weeks.	Other: Placebo

Arm

Intervention/Treatment

Experimental: Metanx

Subjects will take 2 Metanx tablets once daily for 48 weeks.

Other: Metanx

Metanx is a prescription medical food.

Placebo Comparator: Placebo

Subjects will take 2 placebo tablets once daily for 48 weeks.

Other: Placebo

Outcome Measures

Primary Outcome Measures

Change in plasma methylmalonic acid (MMA) levels [16 weeks]

Secondary Outcome Measures

Change in plasma 5-methyltetrahydrofolate levels [16 weeks]
Change in plasma vitamin B6 levels [16 weeks]
Change in plasma vitamin B12 levels [16 weeks]
Change in urine microalbumin/creatinine ratio [48 weeks]
Change in epidermal nerve fiber density [48 weeks]
This neuropathy-specific measure will be evaluated to monitor for signs of disease progression.
Change in neuropathic disability as measured by the Michigan Neuropathy Screening Instrument part B [48 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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Coastal Clinical Research, Inc.	Mobile	Alabama	United States	36608
2	Arizona Research Center	Phoenix	Arizona	United States	85023
3	Clinical Trials, Inc.	Little Rock	Arkansas	United States	72205
4	Collaborative Neuroscience Network, LLC	Long Beach	California	United States	90806
5	Center for Clinical Research, Inc.	San Francisco	California	United States	94115
6	Coastal Connecticut Research, LLC	New London	Connecticut	United States	06320
7	Meridien Research	Bradenton	Florida	United States	34208
8	PAB Clinical Research	Brandon	Florida	United States	33511
9	Suncoast Clinical Research, Inc.	New Port Richey	Florida	United States	34652
10	Renstar Medical Research	Ocala	Florida	United States	34471
11	Suncoast Clinical Research	Palm Harbor	Florida	United States	34684
12	Florida Medical Clinic	Wesley Chapel	Florida	United States	33544
13	North Chattahoochee Family Physicians, LLC	Johns Creek	Georgia	United States	30097
14	Willis-Knighton Physician Network / WKB Family Medicine Associates	Bossier City	Louisiana	United States	71111
15	Tulane University School of Medicine	New Orleans	Louisiana	United States	70112
16	Urgent Care Specialists, LLC dba Hometown Urgent Care & Occupational Health	Dayton	Ohio	United States	45424
17	CRI Lifetree	Philadelphia	Pennsylvania	United States	19139
18	Trinity Clinical Research, LLC	Tullahoma	Tennessee	United States	37388
19	FutureSearch Trials of Neurology, L.P.	Austin	Texas	United States	78731
20	Centex Studies Inc.	Houston	Texas	United States	77062
21	Pioneer Research Solutions, Inc.	Houston	Texas	United States	77098
22	Endeavor Clinical Trials, PA	San Antonio	Texas	United States	78229
23	Northeast Clinical Research of San Anotnio, LLC	Schertz	Texas	United States	78154
24	ClinPoint Trials, LLC	Waxahachie	Texas	United States	75165
25	Strelitz Diabetes Center	Norfolk	Virginia	United States	23510