NCT05785884 · University of Alabama at Birmingham
Diet Interventions: Remitted and Evaluated as Complementary Treatments for Pain
(DIRECTPain)
What this study is about
Knee osteoarthritis (OA) is the most prevalent form of arthritis, a significant cause of disability in the U.S. With an aging population and the rise in obesity rates, the prevalence of knee OA is expected to climb, significantly reducing quality of life (QOL) for those suffering from this debilitating condition.
View original scientific description
Knee osteoarthritis (OA) is the most prevalent form of arthritis, a significant cause of disability in the U.S. With an aging population and the rise in obesity rates, the prevalence of knee OA is expected to climb, significantly reducing quality of life (QOL) for those suffering from this debilitating condition. Current national efforts to reduce analgesic utilization highlight the critical need for safe, effective, and accessible alternatives for pain relief. Low-carbohydrate diets (LCDs) reduce inflammation and pain independent of weight loss, indicating that diet interventions offer a non-pharmacological complementary treatment. However, differences exist in metabolism that are rarely addressed in diet intervention studies. Thus, it is important to assess the potential of different diets in a broad population of chronic pain sufferers to determine the potential of diets to reduce knee OA pain. We have shown that a LCD was associated with reduced evoked knee OA pain, daily pain and oxidative stress when compared to either a USDA diet or a diet-as-usual control. Both experimental diets reduced weight to a similar degree, arguing that diet quality was likely the key factor in pain reduction, as opposed to weight loss. However, previous studies comparing diets have utilized diet prescriptions with less control for adherence to the diets. To overcome this obstacle, and in line with our recent work, we will provide all snacks and meals during the diet intervention to increase adherence and retention in the study, allowing for better control over diet interventions and consistency of foods within each study group. We will recruit adults with knee OA (N=200) to complete our two-phase protocol. Phase 1 will involve a 1-week diet run-up that will allow for quantification of pain measures, psychosocial variables (socioeconomic status, nutritional knowledge, proximity to grocery stores, food insecurity), and diet quality to provide a baseline for comparison. Phase 2 will be a 6-week randomized diet intervention (LCD or USDA diet) in which both groups will be provided with all meals at the direction of study personnel and input from participants. Evoked pain tasks, measures of pain disability, severity, catastrophizing, and interference will be assessed every 3 weeks in addition to QOL measures, mood, and depression. Physiological variables will be assessed through blood draws (inflammatory profile) and dual-energy X-ray absorptiometry scans (DXA; body composition, visceral fat) at the end of Phases 1 and 2. This will be the first study to examine the efficacy of these diets to reduce knee OA pain with an emphasis on interactions with biopsychosocial variables. Changes in all pain measures following Phase 2 will be assessed with respect to published measures of clinically-meaningful differences in pain and disability, as well as for statistical significance. The central hypothesis is that the LCD will improve pain and QOL in participants with knee OA more than the USDA diet, but that both will be beneficial. Specific Aim 1: To investigate the efficacy of the diets to reduce pain and improve QOL. Hypothesis 1: The LCD group will show significantly greater reductions in: a) self-reported pain (\>1.7 in pain intensity) and, b) evoked pain (\>30%) when compared to the USDA diet. Hypothesis 2: The LCD group will show greater improvements in: a) QOL, b) mood, and c) self-reported improvement (\>50% participants reporting "much improved" or "very much improved"). Hypothesis 3 (secondary): Both diets will result in improved pain disability, severity, catastrophizing and pain related fear; the LCD will outperform the USDA diet. Specific Aim 2: To explore individual differences in diet and baseline measures. Hypothesis 1: Baseline diet quality will be negatively associated with baseline pain sensitivity Hypothesis 2: Those reporting greater a) food insecurity and/ or b) proximity to grocery stores will report poorer-quality diets. Specific Aim 3: To determine whether physiological variables contribute to diet effects or lack thereof. Hypothesis 1: Baseline physiological measures (inflammatory profile) will predict: a) pain sensitivity, and b) reductions in pain. Hypothesis 2: Change in physiological measures (inflammatory profile, adiposity, leptin) will be related to: a) change in pain measures, b) change in QOL, c) self-reported improvement and, d) mood.
Interventions
BEHAVIORAL
Diet
A 6 week randomized diet
Primary outcome measures
Western Ontario and McMaster Osteoarthritis Index pain change
Time frame: Baseline (week 0), immediately before the intervention (week 3), 3 weeks after initiating the intervention (week 6), immediately after the intervention (week 9)
The Western Ontario and McMaster Osteoarthritis Index (WOMAC) pain score is a 0-20 score with higher scores reflecting more severe pain. Questions 1-5 are summed to provide a WOMAC pain score. Change scores will be calculated. Greater change scores would reflect more improvement.
BPI pain change
Time frame: Baseline (week 0), immediately before the intervention (week 3), 3 weeks after initiating the intervention (week 6), immediately after the intervention (week 9)
The Brief Pain Inventory (BPI) pain score is a 0-40 score with higher scores reflecting more pain. Questions 3-6 are scored on 0-10 and are summed to provide an overall pain score. Change scores will be calculated.
TUG pain intensity change
Time frame: Baseline (week 0), immediately before the intervention (week 3), 3 weeks after initiating the intervention (week 6), immediately after the intervention (week 9)
Before and after the Timed-Up-And-Go (TUG) task, participants will be asked to rate the intensity of pain in their knee on a 0-100 scale. The difference in the ratings will be considered the evoked pain score. Change scores will be calculated.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- diagnosis of knee OA
- pain in at least 4/7 days/week for the past 3 months (pain of ≥3/10 on 0-10 scale)
- age between 40-75
- average daily consumption of \>100 g carbohydrates (based on Phase 1 food checklist)
- understanding of verbal and written English
- self-identification as either NHB or NHW
- BMI between 25 and 40 kg/m2
Exclusion criteria
- unmedicated diabetes
- unwillingness to follow prescribed diets
- 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
- use of tobacco
- participation in extreme exercise
- knee replacement
Where
- Birmingham, Alabama
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
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Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
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How long does a clinical trial last?
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Data: ClinicalTrials.gov · synced Aug 6, 2025 · Source of record for eligibility and locations