Type 2 Diabetic Peripheral Neuropathy (DPN)
Conditions
Keywords
Metanx, diabetes, neuropathy, folic acid, folate, L-methylfolate, vitamin B6, Pyridoxal 5'-phosphate, vitamin B12, methylcobalamin
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.
Interventions
OTHERMetanx (a medical food)
Metanx one tablet twice a day
OTHERMetanx placebo
Metanx placebo one tablet twice a day
Sponsors
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
Pamlab, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
25 Years to 80 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | NDS scores were taken at 0 (Baseline), 16, and 24 weeks | 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 | Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks | 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 | SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks | 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 | VAS scores were taken at 0 (Baseline) and 24 weeks | 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. |
| Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks | 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. |
| (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | HADS Scores scores were taken at 0 (Baseline) and 24 weeks | 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 | Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks | 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 | Analyte levels were taken at 0 (Baseline) and 24 weeks | (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 | Analyte levels were taken at 0 (Baseline) and 24 weeks | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory markers levels including Potential Antioxidant (PAO) |
| (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | Analyte levels were taken at 0 (Baseline) and 24 weeks | (Exploratory) To determine if Metanx® affects a subject's plasma oxidative stress and inflammatory marker levels, including IL-6 and TNF-α |
Countries
United States
Participant flow
Recruitment details
Of 373 patients screened, 214 entered the study , and 200 completed. The study was conducted at 6 participating U.S. sites
Pre-assignment details
Inclusion criteria included individuals 25 and 80 years of age, documented diabetes Type 2, Peripheral polyneuropathy, adequate lower extremity vascular status, and subject competence. 17 exclusion criteria including an HbA1c \>9, uncontrolled heart or lung disease, and vitamin B supplementation, contributed to the number of screening failures.
Participants by arm
| Arm | Count |
|---|---|
| Metanx Metanx one tablet twice a day | 106 |
| Placebo Placebo one tablet twice a day | 108 |
| Total | 214 |
Baseline characteristics
| Characteristic | Metanx | Placebo | Total |
|---|---|---|---|
| Age Continuous | 62.29 years STANDARD_DEVIATION 8.54 | 62.95 years STANDARD_DEVIATION 9.17 | 62.6 years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 33 Participants | 33 Participants | 66 Participants |
| Sex: Female, Male Male | 73 Participants | 75 Participants | 148 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 106 | 27 / 108 |
| serious Total, serious adverse events | 5 / 106 | 8 / 108 |
Outcome results
Primary
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.
Time frame: VPT was measured a 0 (baseline), and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | Baseline | 32.16 volts | Standard Deviation 13 |
| Metanx | Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | Change from Baseline Week 24 | -1.96 volts | Standard Deviation 13.08 |
| Placebo | Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | Baseline | 33.88 volts | Standard Deviation 14.24 |
| Placebo | Change From Baseline in Vibration Perception Threshold (VPT) at 24 Weeks | Change from Baseline Week 24 | -3.27 volts | Standard Deviation 10.32 |
Secondary
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.
Time frame: VAS scores were taken at 0 (Baseline) and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 | VAS Baseline | 3.26 units on a scale (0-10) | Standard Deviation 2.77 |
| Metanx | Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 | VAS, Change from BL, Week 24 | -0.27 units on a scale (0-10) | Standard Deviation 2.28 |
| Placebo | Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 | VAS Baseline | 3.25 units on a scale (0-10) | Standard Deviation 2.76 |
| Placebo | Change From Baseline in 10-point Visual Analog Scale(VAS) at Week 24 | VAS, Change from BL, Week 24 | -0.03 units on a scale (0-10) | Standard Deviation 2.61 |
Secondary
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.
Time frame: NDS scores were taken at 0 (Baseline), 16, and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | Baseline | 7.51 units on a scale (0-10) | Standard Deviation 2.36 |
| Metanx | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | Change from Baseline Week 16 | -0.78 units on a scale (0-10) | Standard Deviation 2.13 |
| Metanx | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | Change from Baseline Week 24 | -0.47 units on a scale (0-10) | Standard Deviation 2.11 |
| Placebo | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | Baseline | 7.47 units on a scale (0-10) | Standard Deviation 2.17 |
| Placebo | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | Change from Baseline Week 16 | -0.18 units on a scale (0-10) | Standard Deviation 2.24 |
| Placebo | Change From Baseline in Neuropathy Disability Score (NDS)at Week 16 and 24 | Change from Baseline Week 24 | -0.36 units on a scale (0-10) | Standard Deviation 2.14 |
Comparison: Change from Baseline, Week 16p-value: =0.027Mixed Models Analysis
Secondary
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.
Time frame: NTSS-6 scores were taken at 0 (Baseline), 16, and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | Baseline | 3.73 units on a scale (0-6) | Standard Deviation 1.79 |
| Metanx | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | Change from Baseline Week 16 | -0.09 units on a scale (0-6) | Standard Deviation 1.42 |
| Metanx | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | Change from Baseline Week 24 | -0.96 units on a scale (0-6) | Standard Deviation 1.54 |
| Placebo | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | Baseline | 3.45 units on a scale (0-6) | Standard Deviation 2.05 |
| Placebo | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | Change from Baseline Week 16 | -0.40 units on a scale (0-6) | Standard Deviation 1.72 |
| Placebo | Change From Baseline in Neuropathy Total Symptom Score-6 (NTSS-6) | Change from Baseline Week 24 | -0.53 units on a scale (0-6) | Standard Deviation 1.69 |
Comparison: Change from Baseline, Week 16p-value: =0.013Mixed Models Analysis
Comparison: Change from Baseline, Week 24p-value: =0.033Mixed Models Analysis
Secondary
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
Time frame: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total Folate, Change from BL Week 16 | 7.25 nmol/L | Standard Deviation 10.52 |
| Metanx | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total Folate (nmol/L) at Baseline | 42.19 nmol/L | Standard Deviation 9.93 |
| Metanx | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total MMA, Change from BL Week 16 | -56.38 nmol/L | Standard Deviation 102.72 |
| Metanx | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total Folate, Change from BL Week 24 | 7.53 nmol/L | Standard Deviation 10.42 |
| Metanx | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total MMA, Change from BL Week 24 | -63.29 nmol/L | Standard Deviation 107 |
| Metanx | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total methyl malonic acid (MMA) (nmol/L) at BL | 186.16 nmol/L | Standard Deviation 120.11 |
| Placebo | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total MMA, Change from BL Week 24 | -15.42 nmol/L | Standard Deviation 59.9 |
| Placebo | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total Folate (nmol/L) at Baseline | 43.04 nmol/L | Standard Deviation 9.3 |
| Placebo | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total Folate, Change from BL Week 16 | -1.07 nmol/L | Standard Deviation 8.27 |
| Placebo | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total Folate, Change from BL Week 24 | -2.75 nmol/L | Standard Deviation 8.26 |
| Placebo | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total methyl malonic acid (MMA) (nmol/L) at BL | 195.72 nmol/L | Standard Deviation 169.19 |
| Placebo | Change From Baseline in Plasma Marker Levels of Total Folate and Total Methyl Malonic Acid (MMA) at Week 16 and 24 | Total MMA, Change from BL Week 16 | 13.89 nmol/L | Standard Deviation 125.21 |
Comparison: Total Folate, Change from BL, Week 16p-value: =0.0001Mixed Models Analysis
Comparison: Total Folate, Change from BL, Week 24p-value: =0.0001Mixed Models Analysis
Comparison: Total MMA, Change from Baseline Week 16p-value: =0.0001Mixed Models Analysis
Comparison: Total MMA, Change from BL, Week 24p-value: =0.0008Mixed Models Analysis
Comparison: Total Homocysteine, Change from BL, Week 16p-value: =0.0001Mixed Models Analysis
Comparison: Total Homocysteine, Change from BL, Week 24p-value: =0.0001Mixed Models Analysis
Secondary
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
Time frame: SF-36 MCS and SF-36 PCS scores were measured at 0 (Baseline) and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 PCS, Baseline | 40.74 units on a scale (0-100) | Standard Deviation 10.3 |
| Metanx | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 PCS, Change from BL, Week 24 | 0.03 units on a scale (0-100) | Standard Deviation 8.34 |
| Metanx | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 MCS, Baseline | 50.96 units on a scale (0-100) | Standard Deviation 9.87 |
| Metanx | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 MCS, Change from BL, Week 24 | 1.99 units on a scale (0-100) | Standard Deviation 8.57 |
| Placebo | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 MCS, Change from BL, Week 24 | -0.29 units on a scale (0-100) | Standard Deviation 8.48 |
| Placebo | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 PCS, Baseline | 39.03 units on a scale (0-100) | Standard Deviation 9.81 |
| Placebo | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 MCS, Baseline | 52.66 units on a scale (0-100) | Standard Deviation 8.39 |
| Placebo | Change From Baseline in SF-36 MCS and SF-36 PCS at Week 24 | SF-36 PCS, Change from BL, Week 24 | 0.87 units on a scale (0-100) | Standard Deviation 8.21 |
Comparison: SF-36 MCS, Change from BL, Week 24p-value: =0.0306Mixed Models Analysis
Secondary
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
Time frame: Change from Baseline in Plasma Marker Levels at 0 (Baseline), 16, and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | Change From Baseline in Total Homocysteine at Week 16 and 24 | Total homocysteine (µmol/L) at Baseline | 9.71 µmol/L | Standard Deviation 4.29 |
| Metanx | Change From Baseline in Total Homocysteine at Week 16 and 24 | Total homocysteine, Change from BL Week 24 | -2.68 µmol/L | Standard Deviation 2.98 |
| Metanx | Change From Baseline in Total Homocysteine at Week 16 and 24 | Total homocysteine, Change from BL Week 16 | -2.70 µmol/L | Standard Deviation 2.9 |
| Placebo | Change From Baseline in Total Homocysteine at Week 16 and 24 | Total homocysteine (µmol/L) at Baseline | 9.47 µmol/L | Standard Deviation 3.9 |
| Placebo | Change From Baseline in Total Homocysteine at Week 16 and 24 | Total homocysteine, Change from BL Week 16 | 0.58 µmol/L | Standard Deviation 2.58 |
| Placebo | Change From Baseline in Total Homocysteine at Week 16 and 24 | Total homocysteine, Change from BL Week 24 | 0.48 µmol/L | Standard Deviation 2.4 |
Secondary
(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
Time frame: Analyte levels were taken at 0 (Baseline) and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 | hs-CRP (mg/L), Baseline | 6.46 mg/L | Standard Deviation 5.98 |
| Metanx | (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 | hs-CRP, Change from BL, Week 24 | -0.71 mg/L | Standard Deviation 4.05 |
| Placebo | (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 | hs-CRP (mg/L), Baseline | 7.44 mg/L | Standard Deviation 7.23 |
| Placebo | (Exploratory) Change From Baseline in Levels of Hs-CRP at Week 24 | hs-CRP, Change from BL, Week 24 | 0.13 mg/L | Standard Deviation 4.15 |
Secondary
(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
Time frame: Analyte levels were taken at 0 (Baseline) and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | IL-6 (pg/mL), Baseline | 3.66 pg/mL | Standard Deviation 2.91 |
| Metanx | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | IL-6, Change from BL, Week 24 | -0.25 pg/mL | Standard Deviation 2.6 |
| Metanx | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | TNF-a (pg/mL), Baseline | 1.69 pg/mL | Standard Deviation 1.25 |
| Metanx | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | TNF-a, Change from BL, Week 24 | 0.03 pg/mL | Standard Deviation 0.76 |
| Placebo | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | TNF-a, Change from BL, Week 24 | -0.04 pg/mL | Standard Deviation 0.54 |
| Placebo | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | IL-6 (pg/mL), Baseline | 3.68 pg/mL | Standard Deviation 3.01 |
| Placebo | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | TNF-a (pg/mL), Baseline | 2.01 pg/mL | Standard Deviation 2.72 |
| Placebo | (Exploratory) Change From Baseline in Levels of IL-6 and TNF-α, at Week 24 | IL-6, Change from BL, Week 24 | 0.07 pg/mL | Standard Deviation 2.42 |
Secondary
(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)
Time frame: Analyte levels were taken at 0 (Baseline) and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 | PAO (µmol/L), Baseline | 1094.52 µmol/L | Standard Deviation 230.83 |
| Metanx | (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 | PAO, Change from BL, Week 24 | 7.95 µmol/L | Standard Deviation 190.36 |
| Placebo | (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 | PAO (µmol/L), Baseline | 1102.15 µmol/L | Standard Deviation 250.54 |
| Placebo | (Exploratory) Change From Baseline in Levels Potential Antioxidant (PAO) at Week 24 | PAO, Change from BL, Week 24 | 5.29 µmol/L | Standard Deviation 204.92 |
Secondary
(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
Time frame: HADS Scores scores were taken at 0 (Baseline) and 24 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metanx | (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | HADS Depression, Baseline | 4.16 units on a scale (0-21) | Standard Deviation 3.24 |
| Metanx | (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | HADS Depression, Change from BL, Week 24 | -1.03 units on a scale (0-21) | Standard Deviation 2.53 |
| Placebo | (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | HADS Depression, Baseline | 4.42 units on a scale (0-21) | Standard Deviation 3.12 |
| Placebo | (Exploratory) Change From Baseline in the Hospital Anxiety and Depression Scale (HADS) Question Inventory at Week 24 | HADS Depression, Change from BL, Week 24 | -0.45 units on a scale (0-21) | Standard Deviation 2.58 |
Comparison: HADS Depression, Change from BL, Week 24p-value: =0.054Mixed Models Analysis