Investigating Racial Differences in Diet Benefits for Knee Osteoarthritis
Phase: NA
Conditions: Knee Osteoarthritis
Sponsor: University of Alabama at Birmingham

Investigating Racial Differences in Diet Benefits for Knee 
Osteoarthritis 
 
Study Protocol & Statistical Analysis Plan 
 
NCT04343716 
 
08/13/2024 
 
 
Robert Sorge, Associate Professor, Principal Investigator 
University of Alabama at Birmingham 
Birmingham, AL 35294 
 
 

Study Protocol 
A telephone screening interview will be used to assess each participant's OA status and 
assessment of the reported duration of knee OA, current and past treatments, comorbid 
conditions, current medication use, dietary conditions and other exclusion criteria. Eligible, 
participants will be invited to the testing facilities in Campbell Hall for informed consent and 
baseline measures. Following this visit, participants will record daily food consumption for one 
week as well as daily pain ratings. After one week, participants will visit the Clinical Research 
Unit for fasted blood draw and additional testing. Immediately following this session, participants 
will be asked to select one week of meals and snacks from a menu of commercially-available 
meals. Study personnel will record the choices and order the meals to be delivered to the 
participants to initiate the intervention. During the 6-week intervention, participants will be 
contacted by study personnel weekly to place food orders and be instructed to record any 
beverages consumed during the week. Every three weeks, participants will return for testing. At 
the end of 6 weeks, blood will be taken prior to testing/debriefing. 
 
Participants. The investigators will recruit 20 adult women (55-75) with knee OA with equal 
representation across racial groups (10 AA, 10 NHW). Peak prevalence rates for OA are at the 
55-75 years of age, so the investigators feel confident that there will be no trouble recruiting this 
population. Participants will be recruited using existing databases, community flyers and 
community outreach. The feasibility trial used prescribed diets and had an attrition rate of 0% in 
the LCD group. Here, provision of all of the food for the intervention is expected to have lower 
rates of attrition. 
 
Inclusion criteria will include: 
• 
diagnosis of knee OA; 
• 
pain in at least 4/7 days/week for the past 3 months; 
• 
age between 65-75; 
• 
average daily consumption of >100 g carbohydrates; 
• 
understanding of verbal and written English; 
• 
self-identification as either AA or NHW; 
• 
BMI between 25 and 40 kg/m2. 
 
Exclusion criteria will be the following: 
• 
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; 
• 
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. 
 
Diet Intervention. All foods will be provided under the direction of study personnel and will be 
delivered weekly to participants' home address. Weekly contact will maintain retention in the 
intervention and improve adherence. The Dietary Guidelines for Americans suggests 225-325 g 
of carbohydrates/day. Therefore, those participants consuming less than 100 g/day would be 
considered as consuming a reduced-carbohydrate diet and will be excluded. 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). 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. 
Daily or almost-daily consumption of sugar-sweetened beverages was associated with lowered 
optimism in chronic pain sufferers and greater risk for depression in healthy women. 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). LCDs are known to be safe and first-line 
treatments for diabetes. LCDs are also known to reduce inflammatory biomarkers to a greater 
extent than low-fat diets. In fact, a LCD resulted in improved insulin sensitivity as well as 
reduced triglycerides even when weight loss was accounted for. 
 
Anthropocentric Measures. Body weight, height, waist circumference, blood pressure, and heart 
rate will be assessed. 
 
Pain-Specific Questionnaires. Pain and disability will be measured using the Brief pain Inventory 
(BPI) short form and the Western Ontario and McMaster Universities Osteoarthritis Index 
(WOMAC). 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 WOMAC is commonly used in studies of arthritis and has been validated in numerous 
clinical trials. Specifically, the WOMAC allows for assessment of pain and interference, but also 
is specific to aspects of stiffness in the joints not accessed by other surveys. The investigators 
have previously utilized these measures for chronic pain sufferers. These assessments will be 
given at baseline and every 3 weeks. 
 
Evoked Pain Testing. Functional tests will be carried out by study personnel. Participants will 
rate the intensity and unpleasantness of the pain in their affected knee (0-100 scale) prior to and 
immediately following the tests. The numerical rating scale will be anchored at 0 (no pain) and 
100 (worst pain imaginable). Questionnaires will be given between each task to allow for a rest 
period. Task order will be randomized. 
 
Temporal summation will be assessed on the patellar of the affected knee using a nylon 
monofilament (Touch test Sensory Evaluator 6.65) calibrated to bend at 300 g of pressure. 
Participants will provide a pain rating following a single contact of the monofilament, after which 
they will provide another pain rating following a series of 10 contacts (at a rate of one contact 

per second). The change in pain ratings for single versus multiple contacts reflects temporal 
summation. 
 
Repeated chair stands is a portion of the Short Performance Physical Battery. Participants are 
asked to stand from a sitting position five times in a row as fast as possible with arms crossed. 
The time to completion and number of successful stands is scored as the degree of ability. 
 
Timed Up-and-Go is a common task for evaluating pain interference of everyday activities. From 
a seated position, participants will be asked to get up, walk 10 feet, turn and return to the chair. 
Time to complete the task will be recorded. 
 
Timed walk will be the final task included. As in the Short Performance Physical Battery, a 
distance of 15 feet will be marked out on the floor. Participants will complete the distance 
walking at normal gait speed twice and the time to complete each walk will be recorded. 
 
Quality of Life and Emotional State. Quality of Life will be measured using the short form 36 
(SF-36) every 3 weeks. The SF- 36 measures general health status and quality of life across 
eight domains that are relevant for assessment of a diet intervention. The domains include 
physical functioning, role limitations due to physical health, bodily pain, general health 
perceptions, vitality, social functioning, role limitations due to emotional problems, and mental 
health. The SF-36 has demonstrated reliability and validity in older adult populations and in diet 
intervention studies. Depression and mood will be assessed using the Patient Health 
Questionnaire (PHQ-9), which assesses the DSM-IV criteria for depression and can measure 
depression severity and response to intervention. Participants with PHQ-9 scores >15 will be 
referred to University of Alabama at Birmingham (UAB) Psychiatry Services for evaluation, as 
will participants identifying suicidal ideation of any duration on question 9.