Dietary Interventions for Osteoarthritis Pain

(DIRECTPain Trial)

Overseen By Amy M Goss, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Alabama at Birmingham

Must not be taking: Opioids, Metabolism-altering, Anti-hypertensives

Disqualifiers: Diabetes, Eating disorders, Cardiovascular, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

200 Participants Needed

Trial Summary

What is the purpose of this trial?

Knee osteoarthritis (OA) is the most prevalent form of arthritis and race is a risk factor for poor outcomes. Non-Hispanic Black individuals (NHB) report greater disability and pain severity compared to Non-Hispanic Whites (NHW). These differences are reinforced through social and biological mechanisms, ultimately resulting in disparities in pain experience and associated quality of life. National efforts to reduce analgesic utilization highlight the critical need for safe, effective, and accessible alternatives for pain relief for underserved/at-risk populations. Low-carbohydrate diets (LCDs) reduce inflammation and pain independent of weight loss, indicating that diet interventions offer a non-pharmacological alternative. However, racial differences exist in metabolism that are rarely addressed in diet intervention studies. Therefore, a LCD may have greater pain-reducing effects in NHBs and provide an alternative treatment for pain. This will be the first study to examine the efficacy of these diets to reduce knee OA pain with an emphasis on race and interactions with biopsychosocial variables. Aim 1: To investigate the efficacy of the LCD to reduce pain and improve QOL. Hypothesis 1: The LCD group will show significantly greater reductions in: self-reported pain and evoked pain when compared to the USDA diet. Hypothesis 2: The LCD group will show greater improvements in: QOL, mood, and self-reported improvement. Hypothesis 3: Both diets will result in improved pain disability, severity, catastrophizing and pain-related fear; the LCD will outperform the USDA diet. Objective 2: To explore racial differences in diet effects and baseline measures. Hypothesis 1: NHBs will show greater improvements in pain, QOL, and mood. Hypothesis 2: NHBs will report greater food insecurity and less proximity to grocery stores. Hypothesis 3: Diet quality will be negatively associated with baseline pain sensitivity. Objective 3: To determine whether physiological variables contribute to diet effects or lack thereof. Hypothesis 1: Baseline physiological measures will predict: pain sensitivity and reductions in pain. NHBs will show greater inflammation at baseline than NHWs. Hypothesis 2: Change in physiological measures will be related to: change in pain, change in QOL, self-reported improvement and mood. NHWs will show greater reductions in inflammation and adiposity than NHBs.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you use daily opioid pain medications or medications that alter metabolism or digestion.

What data supports the effectiveness of the low-carbohydrate diet treatment for osteoarthritis pain?

Research shows that low-carbohydrate diets can help with weight loss and improve heart health, which might indirectly benefit osteoarthritis by reducing stress on joints and improving overall health. Many people have successfully used these diets to lose weight and maintain it, which could help alleviate joint pain associated with osteoarthritis. ^{1 2 3 4 5}

Is the Atkins diet safe for humans?

The Atkins diet, which is high in fat and low in carbohydrates, may lead to health risks such as high cholesterol and gastrointestinal issues. Long-term use can cause elevated lipid levels and ketosis, which are recognized health risks. ^{5 6 7 8 9}

How does the low-carbohydrate diet treatment for osteoarthritis differ from other treatments?

The low-carbohydrate diet treatment for osteoarthritis is unique because it focuses on reducing carbohydrate intake, which may help manage weight and inflammation, both of which are linked to osteoarthritis symptoms. Unlike other treatments that may focus on medication or physical therapy, this dietary approach targets the potential role of diet in reducing pain and improving joint function. ^{10 11 12 13 14}

Research Team

Robert E Sorge, PhD

Principal Investigator

University of Alabama at Birmingham

Eligibility Criteria

This trial is for English-speaking adults aged 40-75 with knee osteoarthritis, who self-identify as either Non-Hispanic Black or White, have a BMI of 25-40, eat more than 100g of carbs daily, and experience pain most days. Excluded are those on opioids or certain other meds, with recent weight change, major surgery like knee replacement, severe diseases affecting heart/lungs/digestion/metabolism, extreme exercisers or dieters.

Inclusion Criteria

Average daily consumption of >100 g carbohydrates (based on Phase 1 food checklist)

BMI between 25 and 40 kg/m2

Self-identification as either NHB or NHW

Exclusion Criteria

I have lost or gained more than 4 kg in the last month.

I have diabetes and am not taking medication for it.

I have not been hospitalized for an eating or psychiatric disorder in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Participants undergo baseline assessments including anthropometric measures, actigraphy, and diet-related questionnaires

1 week

1 visit (in-person)

Diet Intervention

Participants are randomly assigned to either a Low-Carbohydrate Diet (LCD) or USDA diet, with weekly food delivery and monitoring

6 weeks

Weekly virtual check-ins

Follow-up

Participants are monitored for changes in pain, quality of life, and physiological measures after the intervention

3 weeks

2 visits (in-person)

Treatment Details

Interventions

• Low-carbohydrate diet
• USDA Diet

Trial Overview The study tests if a low-carbohydrate diet can reduce pain and improve quality of life in people with knee OA compared to the standard USDA diet. It will also look at how race might affect these outcomes by focusing on differences between Non-Hispanic Blacks and Whites.

Participant Groups

Group I: Non-Hispanic White Experimental Treatment 2 Interventions

White adults ages 40-75 with knee OA.

Group II: Non-Hispanic Black Experimental Treatment 2 Interventions

Black adults ages 40-75 with knee OA.

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Findings from Research

Participants on low carbohydrate high protein (LCHP) diets, the Zone diet, and conventional hypocaloric diets lost an average of 5.1 kg over 12 weeks, but there were no significant differences in weight or body fat loss among the different diet groups.

High attrition rates were observed across all diet plans, with 43% for LCHP, 60% for the Zone diet, and 36% for the conventional diet, indicating that adherence to these diets may be challenging for individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of weight loss plans on body composition and diet duration. Landers, P., Wolfe, MM., Glore, S., et al.[2006]

In a study of 5677 patients with type 2 diabetes over a median follow-up of 6.3 years, adherence to a healthy lower-carbohydrate diet was linked to a significantly lower risk of mortality, with the third quartile of overall diet score showing a 35% reduced risk compared to the lowest quartile.

Replacing just 2% of energy from carbohydrates with plant-based proteins or polyunsaturated fats was associated with a 23% to 37% reduction in total mortality, highlighting the importance of diet composition in managing long-term health outcomes for individuals with diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Associations of Moderate Low-Carbohydrate Diets With Mortality Among Patients With Type 2 Diabetes: A Prospective Cohort Study. Wan, Z., Shan, Z., Geng, T., et al.[2022]

In a 3-month study involving 30 participants, those on a low-carbohydrate diet lost significantly more weight (6.39 kg) compared to controls (1.05 kg), indicating the diet's efficacy for weight loss.

Despite the weight loss, the low-carbohydrate diet did not lead to increased bone turnover markers compared to controls, suggesting that it may not negatively impact bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a low-carbohydrate diet on bone turnover. Carter, JD., Vasey, FB., Valeriano, J.[2018]

Low-carbohydrate (LC) diets have been shown to be as effective, or even more effective, than low-fat (LF) diets for weight loss and improving cardiovascular risk factors, based on both short-term and long-term studies.

The review suggests that LC diets can positively impact metabolic and hormonal responses, making them a viable alternative for managing obesity, diabetes, and heart disease risk in the American population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diet review: shifting the paradigm. Hite, AH., Berkowitz, VG., Berkowitz, K.[2011]

The Active Low-Carber Forums (ALCF) study involved over 86,000 members, primarily women who were significantly overweight, with many successfully losing over 100 lbs using low carbohydrate diets, particularly the Atkins diet.

More than half of the respondents consulted a physician during their dieting journey, with many receiving support, indicating that low carbohydrate diets can be a viable recommendation for weight control and health improvement by family practitioners.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low carbohydrate diets in family practice: what can we learn from an internet-based support group. Feinman, RD., Vernon, MC., Westman, EC.[2018]

The modified Atkins diet (MAD) effectively reduced seizures in approximately 50% of children with intractable epilepsy and metabolic conditions over a 24-month period.

Importantly, the MAD did not negatively impact growth or bone mass in children, indicating it is a safe long-term treatment option compared to more restrictive diets.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet. Svedlund, A., Hallböök, T., Magnusson, P., et al.[2019]

The Modified Atkins Diet (MAD) significantly improved seizure control in patients with intractable epilepsy, reducing daily seizure frequency from an average of 13.29 to 2.71 over nine months.

Mothers of the patients also experienced a significant improvement in their quality of life across all domains measured, indicating that MAD not only benefits the patients but also positively impacts their caregivers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with MAD on children with epilepsy in Egypt after classic KD failure. El Rashidy, OF., Nassar, MF., El Gendy, YG., et al.[2018]

In a study of 87 children on the modified Atkins diet for epilepsy, 55% of those who continued for over 6 months experienced more than a 50% improvement in seizures, and 35% became seizure-free after an average of 19.9 months.

The diet showed similar efficacy to short-term studies and long-term ketogenic diets, but side effects included increased lipid levels and gastrointestinal issues, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of children treated with the modified Atkins diet. Chen, W., Kossoff, EH.[2017]

The Atkins diet, a high-fat ketogenic diet primarily consisting of animal products, can lead to health risks such as hyperlipidemia and hypercholesterolemia, even in children, due to its carbohydrate-free nature.

Given the potential hazards associated with the Atkins diet, including an increased risk of coronary heart disease, there is a significant concern about the safety of this dietary approach, highlighting the need for controlled studies to better understand its long-term effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Is the Atkins diet safe in respect to health?]. Förster, H.[2006]

High saturated fats, like those found in pork fat, and cholesterol significantly increase the risk of developing osteoarthritis in mice, while unsaturated fats, such as linoleic acid, can counteract these effects.

A high-protein diet may help prevent osteoarthritis in mice, but it can also lead to inflammation in humans, highlighting the complex relationship between diet and joint health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Potential effects of nutrition including additives on healthy and arthrotic joints. I. Basic dietary constituents]. Wilhelmi, G.[2006]

In a study of 89 obese patients with knee osteoarthritis, those on an intensive low-energy diet (LED) lost an average of 10.9 kg (11%) over one year, compared to a 3.6 kg (4%) loss in the control group, indicating significant weight loss efficacy (p<0.0001).

While both groups showed improvement in knee osteoarthritis symptoms, the LED group experienced a notable reduction in pain (7.2 mm difference on the WOMAC scale, p=0.022), suggesting that weight loss can lead to meaningful pain relief in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. Bliddal, H., Leeds, AR., Stigsgaard, L., et al.[2011]

In a study of 129 patients with knee osteoarthritis over 12 weeks, those following a Mediterranean diet experienced significantly greater reductions in pain compared to those on a low-fat or regular diet.

Both the Mediterranean and low-fat diets led to significant weight loss, but the Mediterranean diet was more effective in improving physical function and reducing pain severity, suggesting that its specific dietary components may play a crucial role in managing osteoarthritis symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a Mediterranean Diet Compared with the Low-Fat Diet on Patients with Knee Osteoarthritis: A Randomized Feeding Trial. Sadeghi, A., Zarrinjooiee, G., Mousavi, SN., et al.[2022]

In a study of 77 osteoarthritis patients over 12 weeks, 79% were found to be obese, which was linked to increased pain from osteoarthritis, indicating that weight management could be crucial for pain relief.

The patients had dietary deficiencies in key nutrients like vitamin D and zinc, suggesting that improving nutrition alongside weight loss could enhance their overall management of osteoarthritis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutrient intake and obesity in a multidisciplinary assessment of osteoarthritis. White-O'Connor, B., Sobal, J.[2013]

In a study of 21,901 American adults, higher adherence to the DASH dietary pattern was linked to a lower likelihood of having osteoarthritis (OA), with a significant trend observed across different levels of adherence.

The results suggest that following the DASH diet, which emphasizes fruits, vegetables, and whole grains, may help reduce the risk of developing OA among older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adherence to DASH dietary pattern is inversely associated with osteoarthritis in Americans. Zhang, Y., Francis, EC., Xia, T., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effect of weight loss plans on body composition and diet duration. [2006]

2. United States pubmed.ncbi.nlm.nih.gov

Associations of Moderate Low-Carbohydrate Diets With Mortality Among Patients With Type 2 Diabetes: A Prospective Cohort Study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

The effect of a low-carbohydrate diet on bone turnover. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Low-carbohydrate diet review: shifting the paradigm. [2011]

5. England pubmed.ncbi.nlm.nih.gov

Low carbohydrate diets in family practice: what can we learn from an internet-based support group. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Prospective study of growth and bone mass in Swedish children treated with the modified Atkins diet. [2019]

7. Denmark pubmed.ncbi.nlm.nih.gov

Experience with MAD on children with epilepsy in Egypt after classic KD failure. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Long-term follow-up of children treated with the modified Atkins diet. [2017]

9. Germany pubmed.ncbi.nlm.nih.gov

[Is the Atkins diet safe in respect to health?]. [2006]

10. Germany pubmed.ncbi.nlm.nih.gov

[Potential effects of nutrition including additives on healthy and arthrotic joints. I. Basic dietary constituents]. [2006]

11. England pubmed.ncbi.nlm.nih.gov

Weight loss as treatment for knee osteoarthritis symptoms in obese patients: 1-year results from a randomised controlled trial. [2011]

12. India pubmed.ncbi.nlm.nih.gov

Effects of a Mediterranean Diet Compared with the Low-Fat Diet on Patients with Knee Osteoarthritis: A Randomized Feeding Trial. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

Nutrient intake and obesity in a multidisciplinary assessment of osteoarthritis. [2013]

14. England pubmed.ncbi.nlm.nih.gov

Adherence to DASH dietary pattern is inversely associated with osteoarthritis in Americans. [2021]