Type 2 Diabetic Peripheral Neuropathy (DPN)Phase 4NCT00726713
Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN)
A Phase 4 study testing Metanx (a medical food) in people with Type 2 Diabetic Peripheral Neuropathy (DPN), run by Pamlab, Inc. at 6 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 80 years
- Conditions the study is for
- Type 2 Diabetic Peripheral Neuropathy (DPN)
- What is being tested?
- Metanx (a medical food)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 214 participants
- Where
- 6 sitesUnited States
- Study dates
- Jun 2008to Jun 2011
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 17Show fewer
- 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.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
University of Alabama at Birmingham School of Medicine
Birmingham, Alabama, 35294
Dallas Diabetes and Endocrine Center
Dallas, Texas, 75230
Tulane University Health Sciences Center
New Orleans, Louisiana, 70112
Omaha VA Medical Center
Omaha, Nebraska, 68105
dgd Research, Inc.
San Antonio, Texas, 78229
Scott and White Hospital & Clinic
Temple, Texas, 76504
About this study
Official title: A 24 Week, Double-blind, Placebo-controlled, Multisite Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN)
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.
- Being tested
- Metanx (a medical food), Metanx placebo
- Keywords
- Metanx, diabetes, neuropathy, folic acid, folate, L-methylfolate, vitamin B6, Pyridoxal 5'-phosphate, vitamin B12, methylcobalamin
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metanx (a medical food)Other
Metanx one tablet twice a day
Metanx placeboOther
Metanx placebo one tablet twice a day
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Metanx Receives: Other: Metanx (a medical food) |
| 2 | Placebo comparator | Placebo Receives: Other: Metanx placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: VPT was measured a 0 (baseline), and 24 weeks
Secondary outcomes (10)
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.
Measured: NTSS-6 scores were taken at 0 (Baseline), 16, and 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.
Measured: NDS scores were taken at 0 (Baseline), 16, and 24 weeks
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
Measured: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks
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
Measured: SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks
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".
Measured: VAS scores were taken at 0 (Baseline) and 24 weeks
(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
Measured: Analyte levels were taken at 0 (Baseline) and 24 weeks
(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
Measured: HADS Scores scores were taken at 0 (Baseline) and 24 weeks
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
Measured: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks
(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
Measured: Analyte levels were taken at 0 (Baseline) and 24 weeks
(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)
Measured: Analyte levels were taken at 0 (Baseline) and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2008 (estimated)
- Study startJun 2008
- Primary completionMay 2010
- Study completionJun 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetic Peripheral Neuropathy (DPN)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 214 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pamlab, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- 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
- Responsible party
- Sponsor
- Investigators
- Vivian Fonseca, MD, Principal investigator, Tulane University Health Sciences Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00726713
- Sponsor's protocol ID
- M-001
- Status last verified
- Jul 2013
- First submitted
- 30 Jul 2008
- Last updated
- 30 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 23218892
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A 24 Week, Double-blind, Placebo-controlled, Multisite Study of Metanx® in Subjects With Type 2 Diabetic Peripheral Neuropathy (DPN)
- ClinicalTrials.gov ID
- NCT00726713
- Acronym / sponsor ID
- M-001
- Keywords
- Metanx, diabetes, neuropathy, folic acid, folate, L-methylfolate, vitamin B6, Pyridoxal 5'-phosphate
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 214 participants (actual)
- Lead sponsor
- Pamlab, Inc.Industry (pharma, biotech, devices)
- 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
- Study start
- Jun 2008
- Primary completion
- May 2010 (actual)
- Study completion
- Jun 2011 (actual)
- First posted
- 1 Aug 2008 (estimated)
- Results
- Posted 30 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Metanx (a medical food)Metanx |
| 2 | Placebo comparator | Other: Metanx placeboPlacebo |
Who may qualify
- Ages
- 25 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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:
- The subject is able to understand the information in the informed consent form and is willing and able to sign the consent.
Key exclusion criteria (17 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metanx (a medical food)Metanx one tablet twice a day | Other | 1 |
| Metanx placeboMetanx placebo one tablet twice a day | Other | 2 |
Primary outcome
Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks
Time frame: VPT was measured a 0 (baseline), and 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.
10 secondary outcomes
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
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
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
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
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
(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
(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
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
(Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24
Time frame: Analyte levels were taken at 0 (Baseline) and 24 weeks
(Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24
Time frame: Analyte levels were taken at 0 (Baseline) and 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23218892Fonseca 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.
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Not yet recruitingObservational study
Ultrasound Assessment of Sciatic Nerve and Inferior Gluteal Artery in Diabetic Peripheral Neuropathy(DPN): Association With a Target Gene
Diabetic Peripheral Neuropathy (DPN)
Recruiting
Tai Chi vs. Modified-Otago Exercises for Pain, Balance, and Motor Function in Diabetic Peripheral Neuropathy
Diabetic Peripheral Neuropathy (DPN), Type 2 Diabetes Mellitus (T2DM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vivian Fonseca, MD principal investigator
Tulane University Health Sciences Center
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metanx (a medical food) in people with Type 2 Diabetic Peripheral Neuropathy (DPN), run by Pamlab, Inc. at 6 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks (time frame: VPT was measured a 0 (baseline), and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00726713, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2013.