The Efficacy and Safety of Herbal Medicine Treatment Strategy for Patients With Post-Accident Fatigue

The Efficacy and Safety of Herbal Medicine Treatment Strategy for Patients With Post-Accident Fatigue: A Pragmatic Randomized Controlled Pilot Clinical Trial

This study is a pragmatic randomized controlled pilot clinical trial aimed at evaluating the efficacy and safety of herbal medicine treatment strategy for patients with post-traffic accident fatigue, using an education-only group as the control.

0. Background Over three million traffic accidents occur annually across OECD countries, often resulting in fatigue, insomnia, and dizziness that persist beyond the acute phase. Post-accident fatigue is common even after mild injuries and can greatly hinder recovery and daily functioning. In Korean traditional medicine, it is viewed as a deficiency of qi and blood, for which herbal medicine treatment is used to restore vitality. This study aims to assess whether combining herbal medicine with education improves post-accident fatigue and to explore related body composition changes.

1. Patient Recruitment and Screening Phase

1. Patient Recruitment Forty patients meeting the inclusion/exclusion criteria will be recruited starting from the date of IRB registration. Researchers will use block randomization to allocate participants. After obtaining written consent from patients who meet the criteria, they will be assigned to the study. The probability of assignment to each group will be 1:1.
2. Allocation Concealment and Blinding Since blinding is not feasible for this study, it will be conducted as an open-label clinical trial. However, assessor blinding will be implemented. The evaluator, who will not participate in the intervention and will be blinded to group allocation, will conduct assessments in a separate space before the intervention. This role will be performed by a research nurse or a specialist in training.

2. Treatment and Evaluation Phase

1. Control and Experimental Groups

   - The test group will be divided into the "medicinal herbal medicine group," and the control group will be the "education-only group."

   - To study the additional effects of herbal medicine treatment while maintaining the same conditions for both groups, both groups will receive educational brochures as follows:

   • Subjects in both groups will receive an informational brochure and brief training at their first visit. The brochure will provide information-focused explanations, including the definition and causes of fatigue, post-traumatic fatigue, and the impact of dietary habits and alcohol on fatigue.
   • Subjects in both groups will be eligible to receive acupuncture, cupping therapy, pharmacopuncture, and Chuna therapy, if necessary, to treat aftereffects other than fatigue after a traffic accident. The type and method of treatment will be selected within the scope of current clinical practice at the relevant research institution, based on the subject's symptoms and the clinician's judgment. However, herbal medicine treatment aimed at alleviating traffic accident aftereffects will not be permitted during the study period due to concerns about potential confusion with the interventions in this study. - The supplement group will receive additional supplements based on the medical team's diagnosis and take them twice daily for a total of 28 days.

2. Study Duration and Observation Points

   - The study period for the subjects will be 12 weeks, including a 4-week treatment period and an 8-week follow-up period.

   • The baseline will be the study enrollment date (Week 0), and the primary endpoint will be Week 5.
   • Data will be collected during the treatment period (Weeks 1 and 3), and the follow-up visits (Weeks 5 (primary endpoint), 8, and 12).

3. Data Collection for Evaluation i. Primary Outcome

   - (1) FSS-K (Fatigue Severity Scale - Korean version)

   - The primary outcome is the FSS-K at Week 5, the end of the treatment intervention.

   - The assessment will be conducted at screening, enrollment, and assignment, Weeks 1 and 3 of the treatment period, and at follow-up visits at Weeks 5, 8, and 12.

   ii. Secondary Outcome

   - The following indicators will be assessed at visits during the treatment period (Weeks 1 and 3) and at follow-up visits (Weeks 5 (primary endpoint), 8, and 12).

   - (1) CFQ-K (Chalder Fatigue Questionnaire - Korean version)

   - (2) ISI-K (Insomnia Severity Index - Korean version)

   - (3) K-BDI (Beck Depression Inventory - Korean version)

   - (4) Quality of Life Assessment Scale (EQ-5D-5L)

   - (5) Body Fat Percentage

   • (6) Skeletal Muscle Mass

   • (7) Phase Angle

   • (8) Extracellular Water Ratio

   • (9) Adherence

   • (10) Adverse Effects

     3. Follow-Up Phase After the 4-week treatment period, the subjects will be followed up for 8 weeks to assess symptom changes. Both groups will undergo follow-up visits at 5, 8, and 12 weeks from the date of enrollment, assessing the primary outcome (FSS-K), secondary outcomes (CFQ-K, ISI-K, K-BDI, EQ-5D-5L, body fat percentage, skeletal muscle mass, phase angle, extracellular water content, and medication compliance), and adverse events, identical to those observed during the treatment period.

   The follow-up period after 5 weeks will have a time window of ±5 days. The follow-up period after 8 and 12 weeks will have a time window of ±7 days.

   Both groups will undergo blood tests at 5 weeks from the date of enrollment. The blood test items will be identical to those used during the screening period.

4. Monitoring The principal investigator or a co-investigator with medical judgment, authorized by the principal investigator, will maintain the integrity of the research data and collect and review safety data for the study subjects. Monitoring will be conducted every six months.

1. The safety and rights of the subjects are reported.
2. The clinical study is conducted in compliance with the currently approved research protocol and research management standards.
3. The data are reliable, accurate, and safe.

Inclusion Criteria:

• Men and women aged 40 to 69 years.
• Patients who have been in a traffic accident for 12 to 24 weeks.
• Patients with an average score of 4 or higher on the FSS-K questionnaire.
• Participants who voluntarily agreed to participate in the study and signed a consent form.

Exclusion Criteria:

• Participants diagnosed with and receiving treatment for a specific disease that may cause fatigue (cancer, anemia, thyroid dysfunction, etc.).
• Participants with clinically significant abnormalities in blood tests that may be a major cause of fatigue.
• Participants taking herbal medicine for fatigue relief or have taken health supplements for fatigue relief within the past two weeks.
• Participants with other chronic conditions that may interfere with the treatment effect or interpretation of results: stroke, myocardial infarction, kidney disease, active hepatitis, diabetic neuropathy, dementia, epilepsy, etc.
• Participants currently taking steroids, immunosuppressants, psychiatric medications, or other medications that may affect the study results.
• Participants who are not suitable for herbal medicine treatment. Unsafe: Patients with conditions that may affect drug intake or absorption, those with digestive problems following surgery related to such conditions, or those with severe liver or kidney disease (AST, ALT, γ-GTP, and serum creatinine levels greater than twice the upper limit of normal during screening).
• Are pregnant, planning to become pregnant, breastfeeding, or may be pregnant (e.g., recent missed menstrual periods, irregular menstrual cycles, not using contraception, recently had sexual intercourse, or the investigator determines through medical history that pregnancy is possible).
• Participating in research studies other than observational studies without therapeutic intervention.
• Difficulty completing the consent form.
• Other circumstances in which participation in a clinical trial is deemed difficult by the investigator.