Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT05460845 |
Other study ID # |
IRB-300008971 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
July 1, 2022 |
Est. completion date |
August 28, 2023 |
Study information
Verified date |
August 2023 |
Source |
University of Alabama at Birmingham |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Phantom limb pain (PLP) is defined as pain or discomfort in a missing limb following
amputation, whereas residual limb pain (RLP) is often experienced as pain at the site of
amputation. Unfortunately, PLP can affect as many as 80% of upper- or lower-extremity
amputees, with 40-60% also experiencing RLP. There are many theories regarding the mechanisms
underlying these types of pain, but effective treatments remain elusive .Amputation of a limb
is often accompanied by a traumatic event that can be emotionally devastating. Consequently,
studies have reported high levels of depression in this population, up to 80%. Other studies
have reported elevated levels of depression (70%), suicidality (30%) and posttraumatic stress
disorder (PTSD, 20%) with PTSD being highly correlated with PLP. Thus, it is critical that
effective treatments be employed that address, not only the chronic pain, but the comorbid
conditions as well.
Diet interventions have been utilized as a non-pharmacological method to reduce pain and/or
inflammation. We have shown that a low-carbohydrate diet (LCD) reduced pain independent of
weight loss. Importantly, we observed a reduction in depressive symptomology and improved
quality of life (QOL) following the LCD. Thus, it is reasonable to expect that the LCD may
have beneficial effects of pain experience and also on measures of QOL.
Phase 1: To characterize the dietary habits, pain severity and psychological well-being of
the local amputee population.
Hypotheses: We expect that the local population will show high prevalence of phantom limb
pain (PLP) and/or residual limb pain (RLP). Self-report of depressive symptomology,
poor-quality diet, will coincide with low QOL reports.
Phase 2: To assess the feasibility and efficacy of a low-carbohydrate diet (LCD) to reduce
pain and increase QOL in amputees.
Hypotheses: All participants will complete the 6-week LCD. Compared to baseline, a 6-week LCD
will reduce self-reports of pain and depressive symptoms. Overall QOL will improve over 6
weeks with concomitant improved mood and sleep.
Description:
Phase 1: Baseline Demographics
Participants: We expect to recruit 40 participants (male or female, aged 18-65 years) for
Phase 1. Inclusion criteria will be: PLP/RLP for at least 6 months (>4/10 on visual analogue
scale), amputation at least 6 months prior. Exclusion criteria will include: inability to
read/understand English, current infection at amputation site. We will collect clinical data
related to amputation (cause, date, affected limb, level) and sociodemographic information
(sex, gender, race, income, education, employment status etc.), in addition to a 24-hour diet
recall to assess regular diet habits. Furthermore, we will collect the following:
Pain-Related Questionnaires: Chronic PLP/RLP will be assessed using the Brief Pain Inventory
(BPI), Neuropathic Pain Questionnaire (NPQ), and the McGill Pain Questionnaire - Short Form
(MPQ-SF). The BPI is used to assess the severity of pain and the degree to which that pain
interferes with daily activities. This inventory also allows for reports on medications used
to treat pain. The NPQ is specific to the type of pain commonly experienced in PLP/RLP,
consisting of sensory, affective and sensitivity measures. The MPQ-SF is a standard metric
whereby patients can select descriptors to categorize their pain experience more fully across
sensory, affective, and evaluative dimensions.
QOL-Related Questionnaires: The Short-Form 36 (SF-36) measures general health status and
quality of life across eight domains that are relevant to assessment of a diet intervention.
Depression and mood will be assessed using the Center for Epidemiological Studies -
Depression (CES-D) scale. The CES-D assesses depression as well as sleep, appetite and
loneliness and can be used to identify those at risk for clinical depression (score >16).
Higher scores indicate more depressive symptoms. We will utilize the Pittsburgh Sleep Quality
Index (PSQI) to assess self-reported sleep. We believe that the LCD will increase restful
sleep. The Nottingham Extended Activities of Daily Living Scale (NEADL) assesses regular
household and leisure activities and has been used to measure QOL in amputees.
Psychological Questionnaires: The Acceptance and Action Questionnaire (AAQ) will be used to
assess psychological flexibility. The Cognitive Flexibility Scale (CFS) will assess cognitive
flexibility through ratings of agreement with 12 statements. The Multidimensional
Psychological Flexibility Inventory (MPFI) will assess multiple domains of cognitive
flexibility. The Pain Resilience Scale (PRS) will be used as a specific means to investigate
resilience (behavioral perseverance and cognitive positivity) for those with chronic pain.
Phase 2: Diet Intervention
Participants: Following the collection of baseline demographic information at the Spain
Amputee Clinic, we will recruit 10 individuals (male or female, aged 18-65 years) for our
diet intervention phase. Inclusion criteria will be: PLP/RLP for at least 6 months (>4/10 on
visual analogue scale), amputation at least 6 months prior. Exclusion criteria will include:
inability to read/understand English, current infection at amputation site, unmedicated
diabetes, unwillingness to follow prescribed diet, recent weight change (>4 kg in past
month), currently on a diet, history of eating disorders or other psychiatric disorders
requiring hospitalization within the past 6 months, digestive diseases, difficulty chewing or
swallowing, reliance on others for meal preparation, cardiovascular or pulmonary disease,
daily opioid pain medications, use of medications known to alter metabolism or digestion
(e.g., proton-pump inhibitors), use of anti-hypertensive medications that affect glucose
tolerance, participation in extreme exercise.
Diet Intervention: The LCD is designed to reduce daily intake of carbohydrates. Participants
are directed to reduce their total (not net) carbohydrate intake to ≤ 40 g/day. Meals will be
offered such that no combination of chosen meals will exceed our limit. Fats will not be
restricted, nor will protein (meats, eggs). However, the provision of meals by our study
personnel will allow us to cap the total proteins and fats, reducing this source of
variability. Fruits will be restricted and vegetables permitted in limited quantities (2
cups/day of leafy greens, 1 cup/day non-starchy vegetables, etc.). Participants will be
instructed as to the types and quantities of beverages that are permitted to accompany the
LCD. Artificial carbohydrate-free sweeteners (stevia or sucralose) will be permitted, but
powdered sweeteners (aspartame, saccharin, stevia, sucralose) can only be used in limited
quantities as they contain maltodextrin (1 g of rapidly digesting carbohydrate). It is worth
noting that our LCD is not directed at weight loss, but that we expect that some weight loss
will occur.
Food Provision: Adherence to a LCD is associated with increased quality of life and decreased
pain and disability. However, for a number of participants, diet prescriptions of any type
are dramatic lifestyle changes that require oversight to maintain adherence. To overcome the
difficulties in maintaining the assigned diets, food will be provided weekly using the Shipt
service and local grocery stores. Participants will be given a list of available meals and
will choose one week of meals (breakfast, lunch, dinner, snacks) in consultation with study
personnel to increase adherence and contact time. This service will provide for greater
control over the foods being consumed by the diet groups, though checklists will be required
to document adherence and extra foods/beverages aside from the foods provided. Participants
with persistent poor adherence will be counseled by study personnel and may be removed from
the study.
Diet-Related Questionnaires: The short form of the Household Food Security Scale (HFSS-SF)
will be used to assess food security. At baseline and every 3 weeks, participants will
complete the modified Trait and State Food-Cravings Questionnaire, which is designed to
assess hunger, cravings, and other measures associated with perception of ability to refrain
from eating. At the end of Phase 2, participants will complete a modified version of the
Treatment Satisfaction Questionnaire for Medication (TSQM) to assess attitudes and
satisfaction regarding the dietary prescriptions provided and changes in overall health
achieved.
Anthropometric Measures: Weight will be measured at every visit. The same calibrated scale
will be used for all measurements. Height, waist circumference, heart rate and blood pressure
will also be measured.
Statistical Analysis: Data collected in Phase 1 will be used to characterize levels of pain
and other psychosocial outcome variables within this participant population. Descriptive
statistics will be used to express these data. In Phase 2, feasibility will be determined by
adherence and retention in the study. Preliminary efficacy will be detected by comparison of
various outcome measures across time (baseline, weeks 3 and 6), using repeated measures
analysis of variance. Consequently, we will have 80% power to detect an effect size of 0.44
with our alpha set to 0.05 for single measures outlined above (i.e., SF-36 scores, BPI
scores, etc.). Due to the relatively small sample size and the nature of the pilot, we will
not adjust for multiple comparisons.
Clinically-Meaningful Differences: Group mean differences are not always reflective of
clinically-meaningful differences at the individual level. Therefore, an analysis will be
carried out using published clinically-meaningful differences in baseline pain intensity
score. Briefly, a reduction of ≥1.7 on an 11-point rating scale) is considered
clinically-meaningful. In our feasibility trial, we saw that the LCD was more effective in
improving pain, according to the criteria described above.