Using Breath Tests to Study Gut Sulfur Changes During Dietary Therapy (Sulfur-UC)
Sulfur on the Breath: Using Breath Biomarkers to Monitor Gut Microbial Sulfur Metabolism During Elemental and Reduced Sulfur Dietary Therapy
연구 개요
상태
정황
상세 설명
Purpose To determine whether a short-term elemental diet followed by a reduced sulfur diet is a safe, tolerable, and effective non-pharmacologic strategy to improve clinical outcomes, reduce inflammation, and beneficially modulate the gut microbiome in adults with mild-to-moderate ulcerative colitis. A secondary purpose is to validate breath-based biomarkers as non-invasive tools to monitor sulfur metabolism and disease activity. Breath biomarkers include volatile organic compounds (VOCs) and exhaled breath condensate (EBC) to assess sulfur-related metabolites.
Hypothesis A 2-week elemental diet followed by a 10-week reduced sulfur diet will reduce intestinal inflammation and improve clinical outcomes by shifting the gut microbiome away from pro-inflammatory, sulfur-metabolizing bacteria, resulting in reduced sulfur metabolite production detectable through exhaled volatile organic compounds and exhaled breath condensate.
Justification Despite advances in biologic therapies, many UC patients fail to achieve sustained remission, and current treatments do not address upstream drivers such as diet-microbiome interactions. Elemental diets have demonstrated efficacy in Crohn's disease but remain understudied in UC. Emerging evidence links dietary sulfur, microbial sulfur metabolism, and toxic metabolites to UC pathogenesis. This study addresses critical gaps by testing a feasible dietary intervention and validating non-invasive breath biomarkers for real-time disease monitoring and precision nutrition.
Objectives
- Evaluate the clinical efficacy, safety, and feasibility of an elemental diet followed by an reduced sulfur diet.
- Characterize changes in gut microbiome composition, inflammatory markers, and sulfur-related metabolic outputs.
- Validate breath-based volatile organic compounds and exhaled breath condensate as biomarkers of sulfur metabolism and treatment response.
- Identify microbial and metabolic signatures predictive of dietary response.
Research Design A prospective, randomized, controlled trial in adults with mild-to-moderate UC. All participants complete a 2-week elemental diet, followed by randomization (2:1) to either a reduced sulfur diet group (intervention group) or return to habitual diet group (control group) for 10 weeks. Clinical indices, inflammatory biomarkers, stool microbiome profiles and breath samples are collected longitudinally. The initial 2-week elemental diet is applied uniformly to standardize baseline microbial and metabolic conditions prior to randomization and does not replace or delay clinical care decisions.
Statistical Analysis Primary outcomes will be assessed using within- and between-group comparisons of clinical and biochemical response at week 12. Microbiome and metabolomic data will be analyzed using multivariate and differential abundance methods. Correlations between breath biomarkers, microbiome features, and clinical outcomes will assess sensitivity and specificity.
연구 유형
등록 (추정된)
단계
- 해당 없음
연락처 및 위치
연구 연락처
- 이름: Natasha Haskey, PhD
- 전화번호: 250-807-9597
- 이메일: natasha.haskey@ubc.ca
연구 장소
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British Columbia
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Kelowna, British Columbia, 캐나다, V1V 1V7
- University of British Columbia-Okanagan
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연락하다:
- Natasha Haskey, RD, PhD
- 전화번호: 250-807-9597
- 이메일: natasha.haskey@ubc.ca
-
수석 연구원:
- Natasha Haskey, RD, PhD
-
-
참여기준
자격 기준
공부할 수 있는 나이
- 성인
- 고령자
건강한 자원 봉사자를 받아들입니다
설명
Inclusion Criteria:
Age 19-70 years.
=Diagnosis of mild-to-moderate ulcerative colitis, defined by a partial Mayo score (pMayo) of 2-7.
- Evidence of active inflammation at enrollment, defined as:
- C-reactive protein (CRP) > 5 mg/L; or
- Fecal calprotectin (FCP) > 200 µg/g.
- Receiving stable medical therapy for ulcerative colitis for at least 8 weeks prior to enrollment.
- No corticosteroid use at the time of recruitment.
- Under consideration by the treating physician for treatment escalation or biologic switch due to inadequate response to current therapy.
Exclusion Criteria:
- Partial Mayo score (pMayo) > 7.
- Pregnant or breastfeeding.
- Body mass index (BMI) < 18 kg/m².
- History of an eating disorder.
- Severe psychiatric disorder.
- Severe medical conditions, including:
- Active cancer;
- Significant cardiovascular disease;
- Diabetes mellitus; or
- Severe food allergies.
- Known allergy or intolerance to corn, dextrose, or maltodextrin.
- Antibiotic use within 3 months prior to enrollment.
- Probiotic use within 3 months prior to enrollment.
- Use of herbal anti-inflammatory supplements during the study period, including but not limited to:
- Serrapeptidase;
- Curcumin;
- Boswellia; or
- Bromelain.
- History of major gastrointestinal surgery, including:
- Ostomy;
- Total colectomy; or
- Short bowel syndrome.
- Inability or unwillingness to comply with study procedures, including anticipated travel or other commitments that may interfere with participation.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 하나의
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
|---|---|
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실험적: Reduced Sulfur Diet
Participants will consume a novel elemental formula (mBiota Elemental, Good LFE, Santa Monica, CA) as their sole source of nutrition for two weeks.
followed by a 10-week reduced sulfur diet.
The reduced sulfur diet is designed to limit dietary sources of sulfur-containing compounds that may contribute to hydrogen sulfide production by the gut microbiota.
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Elemental liquid diets (EDs) are a subset of Exclusive Enteral Nutrition (EEN).
Similar to EEN, they are nutritionally complete formulas, but differ in that they consist of free amino acids, monosaccharides, and fatty acids instead of whole, intact macronutrients, which are designed for optimal digestibility and to minimize antigenicity.
EDs have been shown to reduce immune activation, favourably modulate the microbiota, suppress proinflammatory cytokines, support epithelial repair, and exclude common dietary additives that may provoke inflammation.
This diet excludes high sulfur foods (e.g., red meat, seafood, eggs), cruciferous vegetables, dried fruits, and fermented beverages.
It also accounts for sulfate intake from drinking water and processed food additives.
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활성 비교기: Habitual Diet
Participants will complete a 2-week elemental diet intervention followed by a 10-week habitual diet.
Participants will be instructed to resume and maintain their usual dietary intake without specific sulfur-restriction recommendations.
|
Elemental liquid diets (EDs) are a subset of Exclusive Enteral Nutrition (EEN).
Similar to EEN, they are nutritionally complete formulas, but differ in that they consist of free amino acids, monosaccharides, and fatty acids instead of whole, intact macronutrients, which are designed for optimal digestibility and to minimize antigenicity.
EDs have been shown to reduce immune activation, favourably modulate the microbiota, suppress proinflammatory cytokines, support epithelial repair, and exclude common dietary additives that may provoke inflammation.
Participants randomized to the comparator group will continue their usual dietary intake for 10 weeks without specific dietary restrictions.
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Composite clinical and biochemical response
기간: Baseline, Week 2 and week 12
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Composite clinical and biochemical response at week 12, defined as >30% and >1-point reduction in pMayo score from baseline, plus rectal bleeding subscore decrease of >1 or an absolute subscore <1, with fecal calprotectin <250 μg/g and CRP <5 mg/L.
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Baseline, Week 2 and week 12
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Stool Biomarkers
기간: Baseline, week 2 and week 12
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fecal calprotectin, shotgun metagenomics (microbiome composition, sulfur metabolizing bacteria), and targeted metabolomics (e.g., hydrogen sulfide, thiosulfate)
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Baseline, week 2 and week 12
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C-Reactive Protein (CRP) concentration
기간: Baseline, week 2 and week 12
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Serum CRP concentration will be measured to assess systemic inflammation.
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Baseline, week 2 and week 12
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Complete Blood Count (CBC) parameters
기간: Baseline, week 2 and week 12
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CBC parameters, including hemoglobin, white blood cell count, platelet count, and differential counts, will be measured.
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Baseline, week 2 and week 12
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Serum inflammatory biomarker concentrations
기간: Baseline, week 2 and week 12
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Serum concentrations of IL-6, TNF-α, MCP-1, and LBP will be measured individually and reported separately.
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Baseline, week 2 and week 12
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Breath Biomarkers
기간: Baseline, week 2 and week 12
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Volatile Organic Compounds (VOCs) and exhaled breath condensate (EBC) to assess sulfur-containing metabolites and host-microbiota interactions
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Baseline, week 2 and week 12
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Adherence to the Elemental Diet and Reduced Sulfur Diet Intervention
기간: Baseline, week 2 and week 12
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Adherence to the ED intervention will be assessed using a modified Medication Adherence Report Scale questionnaire at each visit, as well as through compliance phone calls and food diaries. Poor adherence will be defined as meeting at least one of the following three criteria:
Adverse events (AEs) will be systematically collected throughout the study using a combination of participant self-reporting, scheduled assessments, and clinical monitoring. |
Baseline, week 2 and week 12
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Change in Quality of Life
기간: Baseline, week 2 and week 12
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Health-related quality of life will be measured using the 12-item short form-12 (SF-12).
The SF-12 comprises two components: physical health and mental health.
Scores range from 0 to 100, where 0 indicates the lowest level of health and 100 the highest.
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Baseline, week 2 and week 12
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Change in Anxiety
기간: Baseline, week 2 and week 12
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Anxiety will be assessed by the GAD-7 (Generalized Anxiety Disorder-7).
It is a self-reported screening tool used to measure the severity of generalized anxiety disorder (GAD) symptoms over the past two weeks.
The total score ranges from 0 to 21.
A score of 10 or higher typically indicates clinically significant anxiety and suggests the need for further evaluation or intervention..
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Baseline, week 2 and week 12
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Change in Depression
기간: Baseline, week 2 and week 12
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Depression levels will be assessed by PHQ-8 (Patient Health Questionnaire-8).
It is a widely used self-report screening tool for assessing the severity of depressive symptoms over the past two weeks.
The total score is the sum of all item responses, ranging from 0 to 24.
A score of 10 or higher indicates the presence of clinically significant depressive symptoms and suggests the need for further evaluation or intervention.
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Baseline, week 2 and week 12
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Change in Weight
기간: Baseline, week 2 and week 12
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Body weight will be measured in kilograms (kg)
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Baseline, week 2 and week 12
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Change in Body Mass Index (BMI)
기간: Baseline, week 2 and week 12
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BMI will be calculated as weight (kg) divided by height squared (m²).
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Baseline, week 2 and week 12
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공동 작업자 및 조사자
수사관
- 수석 연구원: Natasha Haskey, RD, PhD, University of British Columbia
연구 기록 날짜
연구 주요 날짜
연구 시작 (추정된)
기본 완료 (추정된)
연구 완료 (추정된)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
키워드
기타 연구 ID 번호
- H26-00017
- POP25-11968 (기타 보조금/기금 번호: Weston Family Foundation)
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
IPD 계획 설명
IPD 공유 액세스 기준
IPD 공유 지원 정보 유형
- 연구_프로토콜
- 수액
- ICF
- ANALYTIC_CODE
- CSR
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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