What is the recommended approach for nutritional interventions in clinical trials?

Recommended Approach for Nutritional Interventions in Clinical Trials

Feeding trials, in which most or all food is provided to participants, are the recommended approach for nutritional interventions in clinical trials as they offer high precision and provide proof-of-concept evidence for dietary intervention efficacy. 1

Types of Nutritional Intervention Trials

1. Feeding Trials

Feeding trials involve providing food to participants during the intervention period and can be categorized into:

• Fully domiciled trials: Participants reside at the research facility for the entire study duration
• Partially domiciled trials: Participants consume some meals on-site but return home
• Non-domiciled trials: Meals are provided to participants to consume at home 1

2. Dietary Counseling Trials

These involve providing dietary advice without direct food provision and have lower precision but greater clinical translatability.

Key Design Considerations for Feeding Trials

Trial Design Selection

• Crossover design: Preferred when feasible as it reduces intra-individual variability and requires fewer participants
• Parallel design: Used when crossover is not appropriate (e.g., when long-term effects are studied)
• Consider washout periods: Essential in crossover designs to mitigate carryover effects 1

Menu Design and Development

Follow this stepwise approach:

1. Establish diet targets: Define nutrient-specific or food group-specific targets
2. Determine menu cycle duration:
   • 3-day cycle for short-term trials (<1 week)
   • 7-day cycle for longer trials
3. Conceptualize culturally appropriate meals that meet participant preferences
4. Develop core meals based on whether using:
   • Bespoke cooked meals prepared by research team
   • Commercial meal provider options
   • Ready-made supermarket meals 1

Food Provision Methods

Choose one or a hybrid of:

• Fresh food delivered to/picked up by participants for home preparation
• Ready-meals from commercial sources
• Specifically prepared fresh or frozen meals by research team or commercial service 1

Energy Level Considerations

• Offer menu plans at multiple energy levels (e.g., 2000,2400,2800 kcal)
• Or provide a single energy level with instructions for participants to consume consistent proportions 1

Blinding and Control Design

• Double-blinding: Ideal but challenging for whole diet interventions
• Placebo controls: More feasible in feeding trials than counseling trials
• Active controls: Used when comparing to standard practice diets
• Blinding success assessment: Evaluate by asking participants to guess their treatment assignment 1

Implementation Best Practices

For Non-domiciled Trials

• Provide food items requiring minimal preparation
• Use year-round available fresh products
• Use generic brands of packaged foods to ensure availability
• Consider allowances for external meals, specific beverages, and "free foods" 1

Participant Considerations

• Clearly communicate expectations during informed consent
• Provide sample menus with portion sizes
• Detail any restrictions (dining out, travel) associated with participation 1

Outcome Measurement Priorities

While various outcomes may be measured, prioritize:

1. Morbidity: Disease-specific outcomes
2. Mortality: When applicable to the nutritional intervention
3. Quality of life: Patient-reported outcomes

Common Pitfalls and How to Avoid Them

• Adherence challenges: More common in non-domiciled trials; mitigate through simplified meal preparation and on-site dining options
• Blinding difficulties: Use opaque containers and limit contact between participants and blinded researchers
• Menu fatigue: Prevent through appropriate menu cycle duration and culturally appropriate food choices
• Food availability issues: Select year-round available products and have suitable substitutions ready 1

Special Considerations for Clinical Populations

• Recognize that "usual diets" may differ from national averages
• Consider specific dietary requirements related to the clinical condition
• Ensure nutritional adequacy based on sex and age of participants 1

By following these recommendations, researchers can design and implement high-quality feeding trials that provide reliable evidence on the effects of nutritional interventions on health outcomes.