Oral B-Complex Vitamin (B6, B9 and B12) Prevents Low Anterior Resection Syndrome in Rectal Cancer Patients With Hyperhomocysteinemia
Oral B-Complex Vitamin (B6, B9 and B12) Supplementation for the Prevention of Low Anterior Resection Syndrome After Sphincter-Preserving Surgery in Rectal Cancer Patients With Hyperhomocysteinemia: A Randomized Controlled Trial
The goal of this clinical trial is to investigate if taking Oral B-Complex Vitamin (B6, B9 and B12) can help prevent low anterior resection syndrome (LARS) in rectal cancer patients with hyperhomocysteinemia after sphincter-preserving surgery for rectal cancer. LARS is a group of bowel problems that can occur after rectal cancer surgery, including frequent bowel movements, an urgent need to have a bowel movement, constipation, and loss of bowel control.
Our previous research suggests that hyperhomocysteinemia increased the occurrence of LARS. Folic acid, vitamin B6 and vitamin B12 are a safe, widely used way to treat hyperhomocysteinemia.
The main questions this study aims to answer are:
- Does taking Oral B-Complex Vitamin (B6, B9 and B12) lower the rate of LARS 6 months after surgery?
- How does this treatment affect internal anal sphincter (IAS) function?
Researchers will compare Oral B-Complex Vitamin (B6, B9 and B12) with a placebo (a look-alike tablet that contains no vitamins) to see if Oral B-Complex Vitamin (B6, B9 and B12) can help prevent LARS.
Participants will:
- Take B-Complex Vitamin (B6, B9 and B12) every day for 6 months
- Visit the clinic twice ( 3 months and 6 months after surgery) for checkups and tests
- Complete the LARS score questionnaire 6 months after surgery
Visão geral do estudo
Status
Intervenção / Tratamento
Descrição detalhada
Low anterior resection syndrome (LARS) is a cluster of bowel dysfunction symptoms after sphincter-preserving surgery for rectal cancer, including incontinence, urgency, and frequent bowel movements. The Chinese Expert Consensus on the Diagnosis and Treatment of LARS (2025 edition) reports an incidence of 69.8% at 3 months and 62.3% at 6-9 months after low anterior resection. LARS may persist for years and substantially impair quality of life. LARS is multifactorial, involving reduced rectal capacity and compliance, internal anal sphincter dysfunction and nerve injury. No drug or treatment is currently available to prevent LARS.
Hyperhomocysteinemia (HHcy) is defined as a serum homocysteine (Hcy) level above 15 μmol/L. The pooled prevalence of hyperhomocysteinemia (Hcy >15 μmol/L) in China was 25.9%. The prevalence of hyperhomocysteinemia is higher in cancer patients. Hyperhomocysteinemia increases the risk of various cardiovascular and cerebrovascular diseases, including coronary heart disease and stroke.
Our preliminary data showed that, in a single-center cohort of 530 patients who underwent low anterior resection for rectal cancer at Qilu Hospital of Shandong University between December 2023 and December 2025, hyperhomocysteinemia was present in 105 of 205 patients with LARS (51.2%) and in 95 of 325 patients without LARS (29.2%). This suggests hyperhomocysteinemia may be a risk factor of LARS.
In a Sprague-Dawley rat model of low anterior resection, hyperhomocysteinemia shortened colonic transit time and increased fecal water content. Postoperative supplementation with folic acid, vitamin B6 and vitamin B12 lowered serum Hcy and reversed these changes.
In our prospective single-arm pilot study, 80 patients who met the same eligibility criteria received Oral B-Complex Vitamin treatment. No adverse events were observed. After 6 months, majority of patients' Hcy levels returned to normal. LARS occurrence was much lower than 62.3%.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Wei Guo, MD, PhD
- Número de telefone: +86 18560089725
- E-mail: guowei_182@126.com
Estude backup de contato
- Nome: Hao Wu, MD, PhD
- Número de telefone: +86 18560086947
Locais de estudo
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Shandong
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Jinan, Shandong, China, 250012
- Qilu Hospital of Shandong University
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- Aged 18 to 75 years
- Body mass index (BMI) of 18.5 to 28 kg/m2
- Low anterior resection performed for rectal cancer
- Serum homocysteine level between 15 and 50 μmol/L both before and after surgery
- No evidence of tumor recurrence or distant metastasis
- No short-term postoperative complications at the time of enrollment
- Able to resume oral intake after surgery
- Signed written informed consent
Exclusion Criteria:
- History of, or planned, neoadjuvant or adjuvant radiotherapy or chemotherapy
- Other severe chronic diseases, such as cardiovascular or cerebrovascular disease, diabetes mellitus or chronic respiratory disease
- Renal insufficiency, epilepsy, or other gastrointestinal diseases
- Hyperhomocysteinemia caused by inherited defects, such as cystathionine beta-synthase deficiency, methylenetetrahydrofolate reductase (MTHFR) deficiency or hereditary folate malabsorption, screened by detailed medical and family history; highly suspected cases will be referred for specialist diagnosis and excluded
- Participation in any other clinical study within the past 3 months
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Prevenção
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Quadruplicar
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Oral B-Complex Vitamin (B6, B9 and B12)
Participants will take Oral B-Complex Vitamin (B6, B9 and B12) tablets, one tablet orally twice daily, starting after resumption of oral intake following surgery. Serum homocysteine (Hcy) will be measured at 3 months after surgery: if Hcy remains above 15 μmol/L, the full dose will continue for another 3 months; if Hcy has returned to normal, the dose will be reduced to one tablet once daily.Treatment will continue until the 6-month postoperative visit. |
Film-coated oral tablet (0.3 g) registered as a health food in China (filing No. G201937000905), manufactured by Dongying Guangyuan Biotechnology Co., Ltd. Each tablet contains vitamin B6 (pyridoxine hydrochloride) 1.38 mg, folic acid (vitamin B9) 286 μg and vitamin B12 (cyanocobalamin) 3.05 μg. Excipients include corn starch, maltodextrin, microcrystalline cellulose, silicon dioxide, magnesium stearate, calcium carbonate and a film-coating premix. |
|
Comparador de Placebo: Placebo
Participants will take placebo tablets identical in appearance, color, odor and packaging to the Oral B-Complex Vitamin (B6, B9 and B12) tablets, one tablet orally twice daily, starting after resumption of oral intake following surgery. The same homocysteine-based dose-adjustment rules as in the experimental arm will apply, and treatment will continue until the 6-month postoperative visit. |
Oral placebo tablet (0.3 g) containing corn starch and maltodextrin, with no active vitamins, manufactured by Dongying Guangyuan Biotechnology Co., Ltd. under good manufacturing practice. The placebo tablets are identical in appearance, color, odor and packaging to the Oral B-Complex Vitamin (B6, B9 and B12) tablets. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Incidence of Low Anterior Resection Syndrome (LARS)
Prazo: 6 months after surgery (3 months after stoma closure for participants whose protective stoma has not been closed by 6 months after surgery)
|
Proportion of participants with LARS, defined as a total score of 21 or higher on the LARS score questionnaire. The LARS score is a validated 5-item questionnaire on bowel function (Emmertsen and Laurberg, 2012), with a total score ranging from 0 to 42; higher scores indicate worse bowel function (0-20: no LARS; 21-29: minor LARS; 30-42: major LARS). |
6 months after surgery (3 months after stoma closure for participants whose protective stoma has not been closed by 6 months after surgery)
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
LARS Score
Prazo: 6 months after surgery (3 months after stoma closure for participants whose protective stoma has not been closed by 6 months after surgery)
|
Total LARS score (range 0-42; higher scores indicate worse bowel function), compared between groups as a continuous variable. |
6 months after surgery (3 months after stoma closure for participants whose protective stoma has not been closed by 6 months after surgery)
|
|
Serum Homocysteine Concentration
Prazo: Baseline (preoperative), and 3 and 6 months after surgery
|
Serum homocysteine concentration (μmol/L). |
Baseline (preoperative), and 3 and 6 months after surgery
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Systolic Blood Pressure
Prazo: 3 and 6 months after surgery
|
Systolic blood pressure (mmHg) measured in the seated position. |
3 and 6 months after surgery
|
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Diastolic Blood Pressure
Prazo: 3 and 6 months after surgery
|
Diastolic blood pressure (mmHg) measured in the seated position. |
3 and 6 months after surgery
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Anal Resting Pressure
Prazo: 3 and 6 months after surgery
|
Anal resting pressure (mmHg) measured by anorectal manometry. |
3 and 6 months after surgery
|
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Maximum Anal Squeeze Pressure
Prazo: 3 and 6 months after surgery
|
Maximum anal squeeze pressure (mmHg) measured by anorectal manometry. |
3 and 6 months after surgery
|
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Presence of Rectoanal Inhibitory Reflex
Prazo: 3 and 6 months after surgery
|
Proportion of participants with a present rectoanal inhibitory reflex on anorectal manometry. |
3 and 6 months after surgery
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Investigador principal: Wei Guo, MD, PhD, Qilu Hospital of Shandong University
Publicações e links úteis
Publicações Gerais
- Collaboration HLT. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ. 1998 Mar 21;316(7135):894-8.
- Emmertsen KJ, Laurberg S. Low anterior resection syndrome score: development and validation of a symptom-based scoring system for bowel dysfunction after low anterior resection for rectal cancer. Ann Surg. 2012 May;255(5):922-8. doi: 10.1097/SLA.0b013e31824f1c21.
- Esse R, Barroso M, Tavares de Almeida I, Castro R. The Contribution of Homocysteine Metabolism Disruption to Endothelial Dysfunction: State-of-the-Art. Int J Mol Sci. 2019 Feb 17;20(4):867. doi: 10.3390/ijms20040867.
- Bone Health and Nutrition Branch of Chinese Nutrition Society; Chinese Society of Parenteral and Enteral Nutrition; North Chronic Disease Prevention and Treatment Branch of Chinese Geriatric Society. Expert consensus on hyperhomocysteinemia. Electronic Journal of Metabolism and Nutrition of Cancer. 2020;7(3):283-288. doi:10.16689/j.cnki.cn11-9349/r.2020.03.007
- Kato I, Dnistrian AM, Schwartz M, Toniolo P, Koenig K, Shore RE, Akhmedkhanov A, Zeleniuch-Jacquotte A, Riboli E. Serum folate, homocysteine and colorectal cancer risk in women: a nested case-control study. Br J Cancer. 1999 Apr;79(11-12):1917-22. doi: 10.1038/sj.bjc.6690305.
- Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D'Agostino RB, Wilson PW, Wolf PA. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002 Feb 14;346(7):476-83. doi: 10.1056/NEJMoa011613.
- Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999;19:217-46. doi: 10.1146/annurev.nutr.19.1.217.
- Chinese Society of Coloproctology, Chinese Medical Doctor Association. Chinese expert consensus on the diagnosis and treatment of low anterior resection syndrome (2025 edition). China Journal of General Surgery. 2025;34(8):1603-1617. doi:10.7659/j.issn.1005-6947.250357
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Complicações pós-operatórias
- Processos Patológicos
- Distúrbios Nutricionais
- Neoplasias por local
- Neoplasias
- Metabolismo, Erros Inatos
- Doenças Genéticas, Congênitas
- Doenças Metabólicas
- Doenças Intestinais
- Neoplasias gastrointestinais
- Neoplasias do Aparelho Digestivo
- Doenças do aparelho digestivo
- Doenças Gastrointestinais
- Neoplasias Colorretais
- Neoplasias Intestinais
- Doenças retais
- Doenças do cólon
- Síndromes de má absorção
- Metabolismo de Aminoácidos, Erros Inatos
- Avitaminose
- Doenças de Deficiência
- Desnutrição
- Deficiência de Vitamina B
- Doenças e Anormalidades Congênitas, Hereditárias e Neonatais
- Condições Patológicas, Sinais e Sintomas
- Doenças Nutricionais e Metabólicas
- Síndrome de Ressecção Anterior Baixa
- Neoplasias retais
- Hiper-homocisteinemia
- Compostos heterocíclicos, 1 anel
- Compostos heterocíclicos
- Compostos heterocíclicos, anel fundido
- Azoles
- Compostos policíclicos
- Compostos heterocíclicos, 4 ou mais anéis
- Pirróis
- Compostos macrocíclicos
- Tetrapirroles
- Corrinóides
- Vitamina B12
Outros números de identificação do estudo
- KYLL-2026-04-037-1
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Individual participant data are subject to China's Regulations on the Management of Human Genetic Resources and will not be shared publicly. De-identified data supporting the published results may be made available upon reasonable request to the principal investigator, subject to approval by Qilu Hospital of Shandong University and compliance with applicable Chinese regulations.
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