Clinical trial NCT05802121: Akkermansia Muciniphilia and Metabolic Side Effects of ADT
Official title: The Role of Akkermansia Muciniphilia in Combating the Metabolic Effects of Androgen Deprivation Therapy in Men With Metastatic Prostate Cancer
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Prostate Cancer
Metabolic Syndrome
Obesity
Cardiovascular Morbidity
Bone Diseases
Hyperlipidemias
Diabetes
Keywords: prostate cancer
metabolic syndrome
androgen deprivation therapy
microbiome
Akkermansias muciniphilia
cardiovascular disease
Lead sponsor: Western University
Sponsor class: OTHER
First posted: 2023-04-06
Enrollment: 30
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a single-institution, randomized controlled trial involving men ≥18 years of age with metastatic castration-sensitive prostate cancer. This study will require histologic confirmation of prostate adenocarcinoma and radiographic evidence of metastatic disease on conventional imaging (CT or BS). Patients will be randomized 1:1 to receive acetate supplementation or placebo. Our institution sees approximately 200 new metastatic prostate cancer patients each year, therefore, the investigators do not anticipate encountering difficulties with recruitment into this study over a period of 2 years.
Primary purpose: PREVENTION

Brief summary: The overriding objectives of this study are:

1. Primary outcomes:

   1. To confirm that administration of oral acetate increases the proportion of A. muciniphilia in the stool samples of patients with metastatic, castration-sensitive prostate cancer compared to placebo.
   2. To confirm tolerability and assess for side effects of delayed oral acetate supplementation.
2. Secondary outcomes:

   1. To determine if increased counts of A. muciniphilia correlate with improved metabolic parameters and improved bone health.


Eligibility criteria: For inclusion in this study, patients must fulfill all of the following criteria:

1. Men ≥18 years of age with histologically-proven metastatic castration-sensitive prostate adenocarcinoma planned to receive ADT (TNM stage Tany, Nany, M1) (see Appendix I).
2. Must have baseline conventional imaging with CT of the abdomen, and pelvis and bone scan.

Patients fulfilling any of the following criteria are NOT eligible for participation in this study:

1. Age less than 18
2. Primary neuroendocrine prostate cancer
3. Treatment with ADT within the year leading up to enrolment
4. Planned or concurrent use of chromium supplementation for the study duration
5. Planned or concurrent use of apple cider vinegar supplementation for the study duration
6. Unable to provide informed consent or unable to understand or read the English language (unless accompanied by an interpreter)
7. Inadequate liver function (\>2x upper limit of normal)
8. Any other condition, chronic disease, or lifestyle factor, that, in the opinion of the Qualified Investigator, may adversely affect the participant's ability to complete the study or its measures or pose significant risk to the participant
9. Use of antibiotics that cannot be discontinued for a washout period and remain off them for the duration of the trial

Primary outcomes:
measure: Fecal Akkermansia muciniphilia counts
timeFrame: 1 week
measure: Fecal Akkermansia muciniphilia counts
timeFrame: 1 month
measure: Fecal Akkermansia muciniphilia counts
timeFrame: 3 month
measure: Fecal Akkermansia muciniphilia counts
timeFrame: 4 month
measure: Fecal Akkermansia muciniphilia counts
timeFrame: 6 month
measure: Side effects and tolerability
timeFrame: 3 months
Secondary outcomes:
measure: Metabolic parameters: fasting plasma glucose
timeFrame: 3 months
measure: Metabolic parameters: fasting plasma glucose
timeFrame: 6 months
measure: Metabolic parameters: HbA1C
timeFrame: 3 months
measure: Metabolic parameters: HbA1c
timeFrame: 6 months
measure: Metabolic parameters: triglycerides
timeFrame: 3 months
measure: Metabolic parameters: triglycerides
timeFrame: 6 months
measure: Metabolic parameters: LDL cholesterol
timeFrame: 3 months
measure: Metabolic parameters: LDL cholesterol
timeFrame: 6 months
measure: Metabolic parameters: HDL cholesterol
timeFrame: 3 months
measure: Metabolic parameters: HDL cholesterol
timeFrame: 6 months
measure: Metabolic parameters: total cholesterol
timeFrame: 3 months
measure: Metabolic parameters: total cholesterol
timeFrame: 6 months
measure: Metabolic parameters: PSA
timeFrame: 6 months
measure: Metabolic parameters: PSA
timeFrame: 3 months
measure: Metabolic parameters: hemoglobin
timeFrame: 3 months
measure: Metabolic parameters: hemoglobin
timeFrame: 6 months
measure: Metabolic parameters: serum creatinine
timeFrame: 3 months
measure: Metabolic parameters: serum calcium
timeFrame: 3 months
measure: Metabolic parameters: serum calcium
timeFrame: 6 months
measure: Metabolic parameters: alanine transferase
timeFrame: 3 months
measure: Metabolic parameters: alanine transferase
timeFrame: 6 months
measure: Metabolic parameters: aspartate aminotransferase
timeFrame: 3 months
measure: Metabolic parameters: aspartate aminotransferase
timeFrame: 6 months
measure: Metabolic parameters: Insulin resistance index (HOMA IR)
timeFrame: 3 months
measure: Metabolic parameters: HOMA IR
timeFrame: 6 months
measure: Bone health: dp-ucMGP levels
timeFrame: 3 months
measure: Bone health: dp-ucMGP levels
timeFrame: 6 months
measure: Bone health: Vitamin K2
timeFrame: 3 months
measure: Bone health: Vitamin K2
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Western University
name: Melissa Huynh, MD
role: PRINCIPAL_INVESTIGATOR
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