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Ca-Mg Butyrate in GWI (Butyrate)

Primary Purpose

Gulf War Illness, Chronic Fatigue, Neurocognitive Dysfunction

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Cal-Mag Butyrate

Placebo

About this trial

This is an interventional treatment trial for Gulf War Illness focused on measuring SCFA, Gulf War Illness, GWI, Microbiome, Butyric acid, Butyrate

Eligibility Criteria

40 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Gulf war era veteran deployed 40 and 70 years old, in good health by medical history prior to 1990 meeting GWI case definition of CDC and Kansas criteria and
currently have no exclusionary diagnoses (self- reported) that could reasonably explain the symptoms of their fatiguing illness. The severity of illness is moderate to severe, scoring less than 30 of 100 on the physical domain of VSF36 .

Exclusion Criteria:

Untreated schizophrenia,
Untreated bipolar disorder,
Untreated delusional disorders,
Untreated dementias of any type and
active alcoholism or drug abuse.
Medical conditions excluded include (i) organ failure, (ii) defined rheumatologic inflammatory disorders, and (iii) transplant.
Use of Butyrate in any form in the 3 months prior to study drug, medications that would impact gut motility, diarrhea, chronic pain, and immune function e.g., steroids, (Last 3 months)
immunosuppressive drugs or biologic response modifiers within 3 months of study entry will be used as exclusion criteria.
Pregnancy, or planned pregnancy in the next 6 months,
Body mass index more than 35
Specific diets that may have enhanced or enriched fiber or butyrogenic formulations (FODMAP)
Medications that could potentially impact immune function in the past one month will be excluded (e.g., steroids, antibiotics, immunosuppressives;
Medications containing supplement calcium or magnesium butyrate should not be taken for at least 3 months before study entry.
Nutraceuticals that are formulated to impact gut microbiome or immune health) and use of drugs that affect GI motility and use of any antibiotic in the last 2 months.
Known allergy to butyrate supplements or their derivatives such as sodium salts or hydroxy derivatives of butyrate and/or inactive ingredients of active and placebo soft gelatin will also be excluded.
Current evidence of celiac disease or late-stage cirrhosis of the liver, Giardia antigen presence, Clostridium difficile toxin in stool, tissue transglutaminase antibody, recent change in gastrointestinal medications, use of drugs that affects gastrointestinal motility, and use of any antibiotic in the last two months also will be excluded.

Sites / Locations

VA Long Beach Healthcare System, Long Beach, CA
Miami VA Healthcare System, Miami, FL
VA Salt Lake City Health Care System, Salt Lake City, UT

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cal-Mag-Butyrate

Placebo for Cal-Mag-Butyrate

Arm Description

Take oral capsule as directed (600 mg, twice a day for 18 weeks) with or without food.

Outcomes

Primary Outcome Measures

Veterans Short Form 36-Item Health Survey Physical Component Summary

Veterans Health Survey contains 36 items to measure health functioning from the patient's point of view. Qualify of life will be determined per Short Form-36 for Veterans' quality of life Physical component (PCS) summary scales, range from 0 to 100 with 100 being better; 50 is expected population average.

Secondary Outcome Measures

California Verbal Learning Test (CVLT-II)

CVLT-II asks questions about cognitive symptoms related to recall and memory. The CVLT-II is used to measure verbal learning and episodic long-term memory. It assesses learning, short- and long-delayed recall and recognition for a list of 16 shopping items. Subjects are expected to remember a list of words. They are asked to repeat the words remembered 5 times (5 trials). Each of the words correctly remembered, in each trial, is marked as 1 point. The reported data represent the number of correct items for the Trial 1-Trial 5, Short Delay Free Recall, and Long Delay Free Recall. The long-delayed recall is assessed at 20 minutes. The CVLT enables a comprehensive characterization of a participant's memory profile. Scale ranges from 0 to 80 with 80 being the best.

Full Information

NCT ID

NCT05367245

First Posted

May 5, 2022

Last Updated

September 12, 2023

Sponsor

VA Office of Research and Development

Collaborators

Miami VA Healthcare System, VA Salt Lake City Health Care System

1. Study Identification

Unique Protocol Identification Number

NCT05367245

Brief Title

Ca-Mg Butyrate in GWI

Acronym

Butyrate

Official Title

Microbiome Targeted Oral Butyrate Therapy in Gulf War Multisymptom Illness

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

November 1, 2023 (Anticipated)

Primary Completion Date

January 10, 2025 (Anticipated)

Study Completion Date

March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

VA Office of Research and Development

Collaborators

Miami VA Healthcare System, VA Salt Lake City Health Care System

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objective of this clinical trial is to determine if treatment with Butyrate formulation that consists of butyric acid as calcium and magnesium derivatives (Ca-Mg Butyrate) improves the physical function of men and women Veterans suffering from Gulf War Illness (GWI). The primary outcome measure is a change from baseline on the Short Form Health Survey 36-item (VSF-36), with respect to physical functioning and symptoms. The secondary outcome will focus on the drug's role in (a) restoring gut microbiome and virome, (b) decreasing gastrointestinal disturbances (constipation, diarrhea, pain), (c) decreasing chronic fatigue, (d) decreasing systemic inflammation, and (e) a decrease in cognitive deficits.

Detailed Description

Nearly one third of 700,000 military personnel deployed during Desert Shield and Desert Storm (Aug 2, 1990 to July 31, 1991) in the Kuwaiti War Theater are suffering from Gulf War Illness (GWI), an unexplained chronic illness characterized by multiple symptoms. The illness has taken a heavy toll on deployed Veterans' overall quality of life. Recent research has revealed the host gut microbiome's role in gastrointestinal disturbance, systemic inflammation, and neurotrophic abnormalities in Gulf War Illness mouse models. Also, short-chain fatty acids such as butyrate restored a healthy microbiome and improved gut microbial metabolism apart from attenuating GWI symptom persistence in preclinical studies. Butyrate, a nutraceutical endogenously produced in the host gut following bacterial fermentation, has shown promise in gastrointestinal disturbances such as irritable bowel syndrome (IBS) and Inflammatory bowel disease (IBD). This is a randomized, two-group, double-blind, placebo-controlled, Phase II clinical trial. The treatment group will receive microencapsulated butyrate capsules (600 mg twice a day for 18 weeks). The placebo group will receive a matching placebo formulation twice a day for 18 weeks. However, after two weeks of the treatment (20 weeks) there will be a follow up virtual visits. The primary outcome measure for this clinical trial is a change from baseline of VSF-36 and CVLT III test scores with respect to physical and mental functioning and symptoms. The secondary outcome measures include changes from baseline of host-microbiome signature, intestinal permeability assessment, peripheral pro-inflammatory biomarkers, and GWI-associated symptoms IBS, chronic pain, fatigue, sleep issues, and cognitive impairment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gulf War Illness, Chronic Fatigue, Neurocognitive Dysfunction

Keywords

SCFA, Gulf War Illness, GWI, Microbiome, Butyric acid, Butyrate

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

-Drug: Ca-Mg-Butyrate Take oral Capsule as directed (600 mg, two times a day for 18 weeks; 2x600 mg/day for 18 weeks) with food or without food. Other name: Calcium-Magnesium Butyrate, BodyBio Cal-Mag Butyrate -Drug: Placebo Take oral Capsule as directed (600 mg, two times a day for 18 weeks; 2x600 mg/day for 18 weeks) with food or without food. Other Name: Sugar pill, inactive substance

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Masking Description

Quadruple, participants, care provider, investigators and outcome assessor will not have access to blinding. Only research pharmacist to distribute the drug or placebo and study coordinator to keep a confidential and secure records, will have access to the blinding.

Allocation

Randomized

Enrollment

120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Cal-Mag-Butyrate

Arm Type

Experimental

Arm Description

Take oral capsule as directed (600 mg, twice a day for 18 weeks) with or without food.

Arm Title

Placebo for Cal-Mag-Butyrate

Arm Type

Placebo Comparator

Arm Description

Take oral capsule as directed (600 mg, twice a day for 18 weeks) with or without food.

Intervention Type

Drug

Intervention Name(s)

Cal-Mag Butyrate

Other Intervention Name(s)

Bodybio Calcium Magnesium Butyrate

Intervention Description

Supplements

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Placebo Cal-Mag Butyrate

Intervention Description

Only Cal-Mag but no Butyric acid

Primary Outcome Measure Information:

Title

Veterans Short Form 36-Item Health Survey Physical Component Summary

Description

Time Frame

Change from Baseline at 3, 6, 9, 12, 18 and 20 weeks

Secondary Outcome Measure Information:

Title

California Verbal Learning Test (CVLT-II)

Description

Time Frame

Change from Baseline at 9, 18 and 20 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Gulf war era veteran deployed 40 and 70 years old, in good health by medical history prior to 1990 meeting GWI case definition of CDC and Kansas criteria and currently have no exclusionary diagnoses (self- reported) that could reasonably explain the symptoms of their fatiguing illness. The severity of illness is moderate to severe, scoring less than 30 of 100 on the physical domain of VSF36 . Exclusion Criteria: Untreated schizophrenia, Untreated bipolar disorder, Untreated delusional disorders, Untreated dementias of any type and active alcoholism or drug abuse. Medical conditions excluded include (i) organ failure, (ii) defined rheumatologic inflammatory disorders, and (iii) transplant. Use of Butyrate in any form in the 3 months prior to study drug, medications that would impact gut motility, diarrhea, chronic pain, and immune function e.g., steroids, (Last 3 months) immunosuppressive drugs or biologic response modifiers within 3 months of study entry will be used as exclusion criteria. Pregnancy, or planned pregnancy in the next 6 months, Body mass index more than 35 Specific diets that may have enhanced or enriched fiber or butyrogenic formulations (FODMAP) Medications that could potentially impact immune function in the past one month will be excluded (e.g., steroids, antibiotics, immunosuppressives; Medications containing supplement calcium or magnesium butyrate should not be taken for at least 3 months before study entry. Nutraceuticals that are formulated to impact gut microbiome or immune health) and use of drugs that affect GI motility and use of any antibiotic in the last 2 months. Known allergy to butyrate supplements or their derivatives such as sodium salts or hydroxy derivatives of butyrate and/or inactive ingredients of active and placebo soft gelatin will also be excluded. Current evidence of celiac disease or late-stage cirrhosis of the liver, Giardia antigen presence, Clostridium difficile toxin in stool, tissue transglutaminase antibody, recent change in gastrointestinal medications, use of drugs that affects gastrointestinal motility, and use of any antibiotic in the last two months also will be excluded.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Saurabh Chatterjee, PhD

saurabhc@hs.uci.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Jonathan Skupsky

Phone

(562) 826-8000

Jonathan.Skupsky@va.gov

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Saurabh Chatterjee, PhD

Organizational Affiliation

VA Long Beach Healthcare System, Long Beach, CA

Official's Role

Principal Investigator

Facility Information:

Facility Name

VA Long Beach Healthcare System, Long Beach, CA

City

Long Beach

State/Province

California

ZIP/Postal Code

90822

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Saurabh Chatterjee, PhD

saurabhc@hs.uci.edu

First Name & Middle Initial & Last Name & Degree

Saurabh Chatterjee, PhD

Facility Name

Miami VA Healthcare System, Miami, FL

City

Miami

State/Province

Florida

ZIP/Postal Code

33125

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Nancy Klimas, MD

Phone

305-575-7000

Ext

142204

nancy.klimas@va.gov

First Name & Middle Initial & Last Name & Degree

Devra Cohen, MPH

Phone

3055757000

Ext

14214

Devra.cohen@va.gov

Facility Name

VA Salt Lake City Health Care System, Salt Lake City, UT

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84148

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Ashok Tuteja, MD

Phone

801-582-1565

ashok.tuteja@va.gov

First Name & Middle Initial & Last Name & Degree

Catherine Loc-Carrillo, MPH

Phone

8015821565

Ext

4616

catherine.Loc-carrillo@va.gov

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Ca-Mg Butyrate in GWI

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