The Pain in Amputees Reduced by Administration of Diet Examination
Condition: Amputation; Phantom Limb Pain; Residual Limb Pain
MeSH terms: Phantom Limb
Study type: Interventional

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.
    

Detailed 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.
    

Intervention name(s): Low-Carbohydrate Diet
Intervention type(s): Behavioral
Intervention description(s): Using a meal delivery service and a list of prepared meals and recipes, foods/meals will be delivered to participants weekly to maintain daily net carbohydrate intake to less than 40 grams.
Other intervention name(s): LCD
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment