Probiotic Supplementation Reduces Gastrointestinal Symptoms During the Therapy and Improves Therapeutic Response in AL Amyloidosis

Study Overview
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Brief Summary
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The purpose of this clinical trial is to evaluate whether specific probiotic can reduce gastrointestinal symptoms and improves therapeutic response, on a background of Bortezomib+dexamethasone or Bortezomib+dexamethasone combined with daratumumab therapy, for naive AL amyloidosis patients.

Official Title
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Probiotic Supplementation Reduces Gastrointestinal Symptoms During the Therapy and Improves Therapeutic Response in AL Amyloidosis: A Randomized Controlled Trial

Conditions
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Immunoglobulin Light-chain Amyloidosis

Intervention / Treatment
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* Drug: Live Combined Bacillus Subtilis and Enterococcus Faecium Enteric-coated Capsules combined with Bortezomib+Dexamethasone/Bortezomib+Dexamethasone+Daratumumab/single Daratumumab
* Drug: Bortezomib+Dexamethasone/Bortezomib+Dexamethasone+Daratumumab/single Daratumumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Biopsy-proven naive AL amyloidosis Receive at least 1 course of treatment based on Bortezomib+Dexamethasone or Bortezomib+Dexamethasone+Daratumumab therapy At least 1 organ (heart, kidney, liver, etc) involved Agree to participate in the project and sign the informed consent. Exclusion Criteria: Received antibiotics for 3 consecutive days and on in the past 2 months prior to the enrollment Had history of probiotics, prebiotics, immunosuppressants, hormones, and other medications use in the past 3 months that influence the Gastrointestinal Microbiome Had other underlying diseases（malignancy or immune system diseases, etc.） Had history of clearly diagnosed chronic gastrointestinal disease Secondary AL amyloidosis or local AL amyloidosis Other conditions the researcher judged unsuitable for enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Probiotic group<br>Naive al amyloidosis patients receive Bortezomib+Dexamethasone, Bortezomib+Dexamethasone+Daratumumab or single Daratumumab therapy combined with Live Combined Bacillus Subtilis and Enterococcus Faecium Enteric-coated Capsules( 250mg/time, bid,up to 3 months). | Drug: Live Combined Bacillus Subtilis and Enterococcus Faecium Enteric-coated Capsules combined with Bortezomib+Dexamethasone/Bortezomib+Dexamethasone+Daratumumab/single Daratumumab<br>* Naive al amyloidosis patients receive Bortezomib+Dexamethasone, Bortezomib+Dexamethasone+Daratumumab or single Daratumumab therapy combined with Live Combined Bacillus Subtilis and Enterococcus Faecium Enteric-coated Capsules(250mg/time, bid,up to 3 months).<br>* Other names: Live Combined Bacillus Subtilis and Enterococcus Faecium Enteric-coated Capsules + Routine therapy;|
| Active Comparator: Control group<br>Naive al amyloidosis patients receive Bortezomib+Dexamethasone, Bortezomib+Dexamethasone+Daratumumab or single Daratumumab therapy without any probiotics. | Drug: Bortezomib+Dexamethasone/Bortezomib+Dexamethasone+Daratumumab/single Daratumumab<br>* Naive al amyloidosis patients receive Bortezomib+Dexamethasone, Bortezomib+Dexamethasone+Daratumumab or single Daratumumab therapy without any probiotics (Blank Control).<br>* Other names: Routine therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of diarrhea | Increased stool frequency and/or loose or watery stools | Up to 3 months after enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time before diarrhea | Time interval from the start of treatment to the first diarrhea | Up to 3 months after enrollment | 
| Duration of the diarrhea | The time between the start of diarrhea and the last diarrhea. | Up to 6 months after enrollment | 
| Hematological response at 3 and 6 months after enrollment | Hematological response is evaluated according to the difference between Serum free light chains and immunofixation electrophoresis. | Up to 6 months after enrollment | 
| Involved organ response（heart）at 3 and 6 months after enrollment | Involved organ response（heart）is evaluated according to the change of NT-proBNP. | Up to 6 months after enrollment | 
| SF-36 score at 1 month, 3 month and 6 month | The general health condition is evaluated by the 36-item Short-Form. The SF-36 measure consists of 36 items that address the following 8 dimensions: physical pain, mental health, general health, emotional role functioning, social functioning, vitality, and physical and role functioning. Each dimension receives a final score between 0 and 100, with 100 representing the best performance. | Up to 6 months after enrollment | 
| GSRS score at 1 month, 3 month and 6 month | The Gastrointestinal Symptoms are evaluated by Gastrointestinal Symptom Rating Scale. The minimum and maximum values is 15 and 105, respectively. The scores are calculated by taking the mean of the items completed within an individual scale, with higher scores indicating greater severity of symptoms. | Up to 6 months after enrollment | 
| Other adverse events that occurred during the treatment | Adverse events are evaluated according to the CTCAE 5.0. | Up to 6 months after enrollment | 
| Survival status at study endpoints | Survival status（live or dead） | From date of randomization until the date of death from any cause, assessed up to 36 months | 
| Changes of al amyloidosis patients' gut microbiome at 3 months and 6 months after enrollment | The changes of gut microbiome are evaluated by 16sRNA (such as Microbiota α-diversity and β-diversity、Changes in gut microbiota at the phylum and the genus levels、Phylogenetic profiles of the gut microbial communities、Microbial functional alteration、Correlations between significantly different ASVs and clinical characteristics in AL amyloidosis patients.etc.) | Up to 6 months after enrollment. | 
| Severity of the diarrhea | The severity of diarrhea was graded according to the CTCAE 5.0. | Up to 6 months after enrollment | 
| Involved organ response（kidney）at 3 and 6 months after enrollment | Involved organ response（kidney）is evaluated according to the change of 24h proteinuria. | Up to 6 months after enrollment |