Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01690962 |
| Other study ID # |
PCRM DN-1 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
September 17, 2012 |
| Last updated |
September 2, 2014 |
| Start date |
November 2012 |
| Est. completion date |
February 2014 |
Study information
| Verified date |
September 2014 |
| Source |
Physicians Committee for Responsible Medicine |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
United States: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
The purpose of this study is to assess whether, in individuals with diabetic neuropathy, a
low-fat, vegan diet in combination with a vitamin B12 supplement improves pain, sensation
and other subjective symptoms, more effectively than a vitamin B12 supplement with no diet
changes. The principal measure is pain as measured by the following assessment tools:
Michigan Neuropathy Screening Instrument, Norfolk Quality of Life Questionnaire, Neuropathy
Impairment Score - Lower Limbs, Neuropathy Total Symptom Score, Neuropathy Pain Scale,
McGill Pain Questionnaire and Global Impression Scale. The study duration is 20 weeks.
This study also examines the effects of a low-fat, vegan diet on mood, using the Center for
Epidemiologic Studies Depression Scale-Revised, and the Beck Depression Inventory.
Description:
The following determinations will be made at baseline, mid-point, and end of each 20-week
study period, as well as at one-year follow up:
General status, symptoms, and medication accounting. Participants will be asked to report
changes in their health and medication use.
Disease Activity. The following assessments will be used to measure pain and changes in
sensory perception related to diabetic neuropathy:
- Michigan Neuropathy Screening Instrument. The MNSI questionnaire consists of 15
questions followed by a single 8-point clinical examination involving inspection of the
foot, assessment of ankle reflexes, and semi-quantitative determination of vibration
perception.
- Norfolk Quality of Life Questionnaire Norfolk QOL-DN is a 47-item questionnaire
developed by the Eastern Virginia Medical School, Norfolk, VA, for assessing subjects'
perception of the effects of diabetes and diabetic neuropathy. It consists of 28 items
pertaining specifically to to small fiber, large fiber and autonomic nerve function
symptoms, and activities of daily living (ADL).
- Neuropathy Impairment Score for Lower Limbs (NIS-LL) The NIS-LL is the lower limb
component of the full Neuropathy Impairment Score (NIS) and has 3 domains including:
muscle weakness, reflexes, and sensation. The maximum score is 88 points. Based on
experience with and data collected from these clinical trials, the Peripheral Nerve
Society considers a 2 point change on the NIS-LL to correspond to a meaningful change
in clinical status.
- Neuropathy Total Symptoms Score (NTSS-6) Neuropathy total symptom score-6 (NTSS-6) is a
neuropathy sensory symptom scale that is designed to evaluate the frequency and
intensity of individual neuropathy sensory symptoms identified frequently by patients
with DPN. A total of six questions are synthesized to identify and quantify the
specific positive and negative symptoms associated with sensory deficits in patients.
- Neuropathy Pain Scale In order to assess and differentiate qualities of pain, Galer and
Jensen developed the Neuropathic Pain Scale (NPS) in 1997. The NPS is composed of 10
items that assess two global pain domains including pain intensity and unpleasantness,
and six pain qualities, including sharp, hot, dull, cold, sensitive, and itchy pain, in
two dimensions (internal and cutaneous).
- McGill Pain Questionnaire The McGill Pain Questionnaire (MPQ) is used to specify
subjective pain experience using sensory, affective and evaluative word descriptors.
The short form of the McGill Pain Questionnaire (SF-MPQ) contains 11 questions
referring to the sensory dimension of the pain experience and four related to the
affective dimension.
- Global Impression Scale Global impression scale (GIS) is also termed global rating of
change scales (GRC) and was developed to assess patients' overall improvement or
deterioration in a clinical setting, and has been frequently used in musculoskeletal
and chronic pain trials.
Height. Height will be measured at baseline (only) with participants standing barefoot with
their backs to a wall-mounted stadiometer and heels against the wall, recorded to the
nearest 0.5 cm.
Body weight. With participants wearing light, indoor clothing but without shoes, body weight
will be measured to the nearest 0.1 kg, using a digital scale.
Blood pressure. A digital blood pressure monitor and a cuff of a size appropriate to the
participant's arm will be used. The cuff size for each participant will be recorded for
consistency of use at each visit. Participants will be asked to remove all clothing that
covers the location of cuff placement and then rest in a seated position for 5 minutes with
legs uncrossed, without talking or reading. The back and arm will be supported such that the
middle of the cuff on the upper arm is at the level of the right atrium (the mid-point of
the sternum). Three measurements will be taken at 1-minute intervals. The first measurement
will be disregarded, and the mean of the remaining 2 measurements will be calculated.
Serum cholesterol and triacylglycerol concentrations will be measured using the Olympus
Cholesterol Reagent on Olympus Chemistry Analyzers. HDL-cholesterol will be measured
directly using the HDL-C plus 3rd generation test with the Roche direct HDL-cholesterol
assay.Low density lipoprotein cholesterol (LDL-C) concentration will be estimated using the
Friedewald equation. Plasma triglyceride levels will be measured using Olympus Chemistry
analyzers from Quest Diagnostics.
Comprehensive Metabolic Panel. These values will be evaluated at baseline, 20 weeks, and
one-year follow-up.
Hemoglobin A1c. Hemoglobin A1c will be measured in whole blood using the COBAS INTEGRA on
Roche clinical chemistry analyzers.
Glucose. Plasma glucose will be measured using an Olympus Chemistry Analyzer from Quest
Diagnostics, Baltimore, MD, USA.
Urinary albumin and creatinine will be assessed on spot urine samples. Samples for the
albumin assay will be tested using the K-Assay High-Sensitive Microalbumin assay from Quest
Diagnostics.
Apolipoprotein E (APOE): Participants who consent to this aspect of the study will be
genotyped for the ε2, ε3, and ε4 alleles. A sample of approximately 5 ml of the
participant's blood is required and will be drawn simultaneously with the 20-week health
assessment labs. Individuals with diabetes are at greatly increased risk of developing
Alzheimer's disease, and some studies have suggested that the effect of saturated fat intake
on Alzheimer's risk may be most evident in (or even limited to) carriers of the APOEε4
allele. The ApoE protein produced by the APOE gene is a major plasma apolipoprotein and the
primary cholesterol carrier in the brain [62]. As a group, these individuals have higher
plasma LDL concentrations, compared with APOEε3 homozygotes [63] Moreover, APOE status may
influence the relationship between dietary intake and plasma lipid concentrations [63]. APOE
determination may provide useful information as to who benefits from dietary changes that
aim to modify plasma lipid concentrations, with implications for subsequent risk of
cardiovascular disease and Alzheimer's disease. The blood test will be drawn once, at the
20-week health assessment only. This test will be optional. If participants decide not to do
the test, it will not affect their status in the study. The blood samples that are collected
will be used for APOE allele testing for this study only. All samples will be destroyed
after analysis and no part of the specimen will be retained per policy of Quest Diagnostics.
Genotyping for Taq1 A and Taq1B polymorphisms. Participants who consent to this aspect of
the study will be genotyped for the A1 and B1 alleles, using the PCR method [64] A sample of
approximately 5 ml of the participant's blood is required and will be drawn simultaneously
with the 20-week health assessment labs. Studies suggest that the A1 allele of the Taq1A
polymorphism (rs1800497), located ≈10 kb downstream of the D2 dopamine receptor (DRD2) gene,
may influence dietary behavior and response to treatment. Individuals with the A1 allele
generally have a lower-than-normal complement of dopamine receptors (DRD2) in the human
brain, and are more likely than others to engage in smoking, substance abuse, and compulsive
gambling [65]. The prevalence of A1 and B1 alleles of the DRD2 gene is strongly associated
with severe alcoholism [66]. Further, the A1 allele is also common among obese individuals
[67]. We identified this allele in approximately half of individuals with type 2 diabetes
participating in a research study [68]. The possibility that genetic factors may influence
dietary behavior may mean that extended support is essential for facilitating dietary
transitions among many, if not all, individuals with diabetes. In group settings, support
can be engaging and cost effective. The blood test will be drawn once, at the 20-week health
assessment only. This test will be optional. If participants decide not to do the test, it
will not affect their status in the study. The blood samples that are collected will be used
for TaqA1 allele testing for this study only. All samples will be destroyed after analysis
and no part of the specimen will be retained per policy of The Biological Samples Processing
Core Facility (BSPC) at the University of California, Los Angeles (UCLA).
Skin biopsy. A single skin biopsy (3 millimeters in diameter and 4 millimeters in depth)
will be removed from one of three sites on the leg at baseline and 20 week health
assessment, as well as at one year follow up. The epidermal nerve fiber density test is the
only objective test currently available for assessing small fiber neuropathy. A physician or
experienced health care professional will clean the skin with alcohol pads and anaesthetize
the skin by administering 2% lidocaine with epinephrine. The biopsy will be performed using
a 3mm disposable, circular punch. The biopsies will be immediately placed in a fixative
container, and then placed into a cooler with an ice pack. The samples will then be shipped
for analysis.
2-day dietary record: A 2-day dietary record will be used to assess macro- and micronutrient
intakes. Participants will be given the option to complete a manual or online version
(online: http://riskfactor.cancer.gov/tools/instruments/asa24/) for collecting and
calculating diet and nutrient intake. Participants will need Internet access if they choose
to do an online version. If necessary, digitized records will be analyzed using Nutrition
Data Systems for Research software (University of Minnesota), by a registered dietitian
certified by the Nutrition Coordinating Center.
24-Hour Multi-Pass Dietary Recalls. At weeks 3 and 12, a registered dietitian will make
unannounced telephone calls to each participant to administer a 24-hour diet recall, using a
multi-pass approach (Nutrition Coordinating Center, University of Minnesota, Minneapolis,
MN). These recalls will not be subjected to statistical analysis, but will allow the
investigators to check for poor adherence. The ASA-24 is a software tool developed by
National Cancer Institute. It enables automated and self-administered 24-hour dietary
recalls. The format and design of ASA-24 are based on a modified version of the
interviewer-administered Automated Multiple Pass Method (AMPM) 24-hour recall developed by
the U.S. Department of Agriculture. Participants will be provided a user name, password, and
link to the ASA-24 online diet recall Web site.
The Eating Inventory is a highly reliable 51-item questionnaire providing quantitative
measures of dietary restraint, disinhibition, and hunger. It will serve as a gauge of ease
in adapting to the intervention diet.
The International Physical Activity Questionnaire short form assesses recent physical
activity patterns. The method is highly reliable; an assessment of test-retest repeatability
produced a correlation of 0.8.
The Clinical Epidemiologic Studies Depression Scale-Revised (CESD-R) assesses mood. The
CES-D is a 20-item self-report measure designed originally for use among the general
population. It measures the frequency with which participants have experienced a specific
symptom within the preceding week, using a four-point rating scale.
The Beck Depression Inventory II (BDI-II) assesses mood. It is the most widely used
instrument for detecting depression. The questions on the BDI-II are in alignment with
DSM-IV criteria. Each item is a list of four statements arranged in increasing severity
about a particular symptom of depression.
Overall quality of life will be assessed using the SF-36, which is a brief health survey
with 36 questions. The SF-36 provides psychometrically-based physical and mental health
summary measures. The SF-36 is a general measure that has been administered across various
age groups, disease spectra, and treatment regimens. Items on the SF-36 are scored on a
scale of 0-100, with a higher score indicating better health-related quality of life.
Medications. Participants in both groups will be asked to keep their medications constant
and to add no new nutritional supplements to their current medication regimen, except as
recommended by their personal physicians.
The interventions for the diet and supplement group and supplement-only group are described
below:
- The diet and supplement group will be asked to follow a low-fat, vegan diet and take a
daily vitamin B12 supplement of 1000mcg of methylcobalamin for 20 weeks. According to
the American Dietetic Association, vegan and vegetarian diets meet all nutritional
requirements when appropriately planned.The diet consists of whole grains, vegetables,
legumes, and fruits, with no restriction on energy intake. Animal products, added oils,
and sugars will be excluded. In choosing grain products and starchy vegetables (e.g.,
bread, potatoes), participants will be encouraged to select those retaining their
natural fiber and having a glycemic index <70, using tables standardized to a value of
100 for glucose. No meals will be provided. Participants will handle their own food
preparation and purchases, with guidance from the research team.
- Participants will be provided with a commercially available supplement containing
vitamin B12 and asked to take it daily during the study. Should they wish to continue
the diet thereafter, they will be counseled to use any standard multivitamin or other
reliable source of vitamin B12.
- The supplement-only group will follow an unrestricted diet, but will be given the
identical vitamin B12 supplement of 1000mcg of methylcobalamin as the diet group.
Before randomization, participants will be told that they will either be assigned to a diet
and supplement intervention group or a supplement-only group.
For both groups, alcoholic beverages will be limited to one per day for women, and two for
men.
