PATM: Microbial Basis of Systemic Malodor and "People Allergic To Me" Conditions

• Sponsor: Mebo Research, Inc. (Other)
• Overall Status: Completed
• CT.gov ID: NCT03582826
• Collaborator: uBiome (Other), Aurametrix (Other)
• Enrollment: 125
• Locations: 2
• Arms: 2
• Actual Duration (Months): 19.8
• Patients Per Site: 62.5
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

The purpose of this study is to identify microbial signatures associated with remission and recurrence of idiopathic malodor and PATM conditions.

Condition or Disease	Intervention/Treatment	Phase
Nutritional and Metabolic Diseases	Behavioral: Nutritional counselling; Behavioral: Stress-reduction counseling	N/A

Detailed Description

Human odorprints, mostly owing to the microbiome, have proven their value as biomarkers of health and environmental exposures. In recent years, microbial networks responsible for localized malodors such as halitosis or axillary odor have been mapped by using next generation sequencing approaches. Intestinal microbes responsible for psychologically debilitating systemic malodor (whole-body and extraoral halitosis), however, remain to be identified. Even a relatively straightforward disorder of choline metabolism trimethylaminuria (TMAU) is thought to exhibit complex host-gene microbiome interactions and has not been sufficiently studied.

Proposed controlled pilot study aims to explore the dynamics of microbial communities in remission and flare-up periods. Better knowledge of the important aspects of disease fluctuation should enhance patient care and, combined with our prior data, will help to develop new therapies and treatments.

Study Design

• Study Type: Interventional
• Actual Enrollment: 125 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: Dynamics of the Gut Microbiota in Idiopathic Malodor Production
• Actual Study Start Date: Jun 16, 2018
• Actual Primary Completion Date: Jun 16, 2019
• Actual Study Completion Date: Feb 10, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MEBO/PATM cohort Nutrition counselling and stress-management counselling behavioral interventions will be given to minimize subjects symptoms and observe corresponding changes in their microbiomes. The following subcohorts were formed for analyses of different outcomes: MEBO and PATM subcohorts, TMAU positive and negative subcohorts, Active MEBO, Active PATM, Regression and Remission; MEBO/PATM Cohort that Submitted Gut Samples, MEBO/PATM cohort that answered QoL survey, MEBO/PATM Subcohort that observed and documented both flareups and improvements.	Behavioral: Nutritional counselling; Behavioral nutritional counselling delivered via the Internet.; Behavioral: Stress-reduction counseling; The psycho-behavioral intervention includes administering questionnaires and monthly maintenance psychological support delivered via the Internet.
No Intervention: non-MEBO cohort Data volunteers that never experienced episodes of uncontrollable socially debilitating metabolic body odor (MEBO) or PATM

Outcome Measures

Primary Outcome Measures

1. Gut Microbiome [1 year]

   Abundance [operational taxonomic units]

Secondary Outcome Measures

1. Quality of Life [Score] [1 year]

   QoL: Scores range from 20 (lowest level of satisfaction with life) to 150 (maximal life satisfaction). Quality of life (QOL) will be measured with MEBO quality of life assessment questionnaire, a new tool designed on the basis of the Halitosis Associated Life-quality Test (HALT), Dermatology Life Quality Index (DLQI) and WHOQOL-100 questionnaires. Most questions were devised with a Likert scale of 0-5 where a higher score indicated a higher quality of life. Scores for five negatively framed questions are transformed to positively framed questions. Total QOL score (minimum score of 20 and maximum score of 150) is computed based on four aspects of QOL: physical health, psychological health, social support and environment.

2. Idiopathic Malodor Episodes [1 year after study enrollment]

   The number of flareups after study enrollment

3. Change in Fecal Microbiome Composition Between Flare-ups and Improvements [1 year]

   The fecal microbial composition will be measured via taxonomic profiling using 16S ribosomal RNA gene amplicon sequencing of submitted gut samples

4. Alpha Diversity [1 year]

   Alpha (within-sample) diversity measure using microbial abundance information in a phylogenetic framework. Represented by abundance-weighted phylogenetic entropy.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 110 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• idiopathic malodor or PATM symptoms experienced over a period of several months or years

• able to read and understand the study information

• willing and able to comply with questionnaires, nutritional recommendations, and other study procedures

Exclusion Criteria:

• consistent inability to communicate and process things related to their symptoms

• consistent inability to distinguish physical symptoms from pure emotional reactions

• lack of motivation to start feeling better

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	MeBO Research	Miami	Florida	United States	33175
2	MeBO Research LTD	London	England	United Kingdom	W10 5LE

Sponsors and Collaborators

• Mebo Research, Inc.
• uBiome
• Aurametrix

Investigators

• Principal Investigator: Irene Gabashvili, PhD, MeBO Research

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 6, 2018
• Informed Consent Form - Jul 12, 2018

More Information

Additional Information:

• uBiome Awards Grant to MEBO Research

Publications

None provided.

• Responsible Party: Mebo Research, Inc.
• ClinicalTrials.gov Identifier: NCT03582826
• Other Study ID Numbers: 201805110018MEBO
• First Posted: Jul 11, 2018
• Last Update Posted: Jan 5, 2021
• Last Verified: Dec 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mebo Research, Inc.: systemic malodor; body odor; bad breath; PATM; microbiome; TMAU; Malabsorption; Dysbiosis
• Additional relevant MeSH terms: Metabolic Diseases

Study Results

Participant Flow

Arm/Group Title	MEBO/PATM Cohort	Non-MEBO/PATM Cohort
Arm/Group Description	The cohort is individuals who experienced symptoms of idiopathic malodor (MEBO) and/or PATM ("people allergic to me" condition)	Individuals that never experienced MEBO or PATM symptoms that donated their gut microbiome samples
Period Title: Overall Study
STARTED	119	6
COMPLETED	78	6
NOT COMPLETED	41	0

Baseline Characteristics

Arm/Group Title	MEBO/PATM Cohort	Non-MEBO/PATM Cohort	Total
Arm/Group Description	The cohort is 119 individuals who experienced symptoms of idiopathic malodor (MEBO: 70 participants) and/or PATM ("people allergic to me" condition: 39 participants)	6 data volunteers that never experienced episodes of uncontrollable socially debilitating odor or PATM.	Total of all reporting groups
Overall Participants	119	6	125
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40 (12)	40 (20)	40 (13)
Sex: Female, Male (Count of Participants)
Female	79 66.4%	1 16.7%	80 64%
Male	40 33.6%	5 83.3%	45 36%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	70 58.8%	5 83.3%	75 60%
United Kingdom	10 8.4%	0 0%	10 8%
Argentina	4 3.4%	0 0%	4 3.2%
Brazil	4 3.4%	0 0%	4 3.2%
Burkina Faso	1 0.8%	0 0%	1 0.8%
Canada	5 4.2%	0 0%	5 4%
Colombia	1 0.8%	0 0%	1 0.8%
France	1 0.8%	0 0%	1 0.8%
Hong Kong	2 1.7%	0 0%	2 1.6%
Italy	1 0.8%	0 0%	1 0.8%
Kenya	2 1.7%	0 0%	2 1.6%
Mexico	1 0.8%	0 0%	1 0.8%
Morocco	1 0.8%	0 0%	1 0.8%
Netherlands	1 0.8%	0 0%	1 0.8%
Nigeria	3 2.5%	0 0%	3 2.4%
Pakistan	1 0.8%	0 0%	1 0.8%
Peru	2 1.7%	0 0%	2 1.6%
Philippines	1 0.8%	0 0%	1 0.8%
Portugal	1 0.8%	0 0%	1 0.8%
South Africa	1 0.8%	0 0%	1 0.8%
Spain	5 4.2%	1 16.7%	6 4.8%
Sweden	1 0.8%	0 0%	1 0.8%
TMAU status (Count of Participants)
Primary TMAU	23 19.3%	0 0%	23 18.4%
Secondary TMAU	12 10.1%	0 0%	12 9.6%
Negative TMAU test result	26 21.8%	0 0%	26 20.8%
Not tested for TMAU	58 48.7%	6 100%	64 51.2%
PATM status (Count of Participants)
PATM with or without MEBO	60 50.4%	0 0%	60 48%
MEBO	59 49.6%	0 0%	59 47.2%
neither MEBO nor PATM	0 0%	6 100%	6 4.8%

Outcome Measures

1. Primary Outcome

Title	Gut Microbiome
Description	Abundance [operational taxonomic units]
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Study volunteers that submitted gut microbiome samples (84 out of 125 enrolled)

Arm/Group Title	MEBO/PATM Cohort That Submitted Gut Samples	Non-MEBO/PATM Cohort
Arm/Group Description	Participants who had experienced uncontrollable socially debilitating odor or PATM symptoms and submitted at least one gut sample for analysis (78 out of 119 in MEBO/PATM cohort)	Samples of volunteers that never experienced episodes of uncontrollable socially debilitating odor or PATM.
Measure Participants	78	6
Measure samples	217	16
Phylum Firmicutes	52	64
Phylum Bacteroidetes	25	33
Phylum Tenericutes	0.04	0.35
Phylum Actinobacteria	3.73	3.37
Phylum Proteobacteria	4.64	3.70

2. Secondary Outcome

Title	Quality of Life [Score]
Description	QoL: Scores range from 20 (lowest level of satisfaction with life) to 150 (maximal life satisfaction). Quality of life (QOL) will be measured with MEBO quality of life assessment questionnaire, a new tool designed on the basis of the Halitosis Associated Life-quality Test (HALT), Dermatology Life Quality Index (DLQI) and WHOQOL-100 questionnaires. Most questions were devised with a Likert scale of 0-5 where a higher score indicated a higher quality of life. Scores for five negatively framed questions are transformed to positively framed questions. Total QOL score (minimum score of 20 and maximum score of 150) is computed based on four aspects of QOL: physical health, psychological health, social support and environment.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Study participants from MEBO/PATM cohort that answered QoL survey (71 out of 119 in MEBO/PATM cohort). Since QOL questionnaire was administered multiple times for each participant, type of units analyzed is number of QoL submissions. Non MEBO/PATM cohort did not participate in this intervention.

Arm/Group Title	Subjects With Active MEBO/PATM	Subjects in Regression or Remission
Arm/Group Description	Individuals experiencing uncontrollable episodes of MEBO or PATM who submitted responses to Quality of Life (QoL) questionnaire.	Individuals self-describing themselves as being in remission or regression of MEBO/PATM (experiencing fewer and less severe flareups or disappearance of the symptoms) who submitted responses to QoL questionnaire.
Measure Participants	64	7
Measure QoL entries	154	34
Mean (95% Confidence Interval) [score on a scale]	57	97

3. Secondary Outcome

Title	Idiopathic Malodor Episodes
Description	The number of flareups after study enrollment
Time Frame	1 year after study enrollment

Outcome Measure Data

Analysis Population Description

Individuals from MEBO/PATM cohort who submitted at least one gut microbiome sample accompanied by a QoL survey. Non-MEBO Cohort is not included since they never experienced MEBO/PATM flareups.

Arm/Group Title	Subjects With Active MEBO/PATM	Subjects in Regression or Remission
Arm/Group Description	Observations of individuals experiencing uncontrollable episodes of malodor or PATM	Observations of individuals self-reporting remission or regression of MEBO/PATM (lessening of the severity or disappearance of the symptoms)
Measure Participants	64	7
Measure observations	154	34
severe flareups	81	7
moderate flareups	27	12
remission episodes	6	12
not sure	40	3

4. Secondary Outcome

Title	Change in Fecal Microbiome Composition Between Flare-ups and Improvements
Description	The fecal microbial composition will be measured via taxonomic profiling using 16S ribosomal RNA gene amplicon sequencing of submitted gut samples
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Study participants that submitted two or more microbiome samples (each accompanied by answers to QoL questionnaire) and observed improvement of their symptoms (22 participants that documented their improvement out of 119 participants in MEBO/PATM cohort). Participants from "Non-MEBO Cohort" are not included since they did not participate in the intervention; there was no difference between their entries in terms of flareups or improvements of MEBO/PATM conditions.

Arm/Group Title	MEBO/PATM Subcohort After Flare-up	MEBO/PATM Subcohort After Improvement
Arm/Group Description	study participants who experienced flare-ups of MEBO/PATM followed by improvements of their condition documented by corresponding gut samples and QoL questionnaire responses (22 out of 119 in MEBO/PATM cohort)	same study participants who experienced improvement in MEBO/PATM status after flare-ups of this condition and submitted corresponding gut samples and QoL questionnaire responses to document their improvement (22 out of 119 in MEBO/PATM cohort)
Measure Participants	22	22
Measure samples	43	43
Selected dermatological bacteria, normalized counts	162	15
Corynebacteriales order, normalized counts	302	91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MEBO/PATM Cohort That Submitted Gut Samples, Non-MEBO/PATM Cohort
	Comments
	Type of Statistical Test	Superiority
	Comments	Paired Wilcoxon Signed-Rank Tests
Statistical Test of Hypothesis	p-Value	0.02
	Comments	Original p-value for dermatological bacteria was 6e-05. It was adjusted first by applying centered log-ratio (CLR) transformation approach then by false discovery rate (FDR) correction for multiple comparisons by using Benjamini-Hochberg Procedure.
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Final Values)
	Estimated Value	79
	Confidence Interval	(2-Sided) 95%; 26 to 163
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Alpha Diversity
Description	Alpha (within-sample) diversity measure using microbial abundance information in a phylogenetic framework. Represented by abundance-weighted phylogenetic entropy.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Participants that submitted valid stool samples. Since 16 individuals who observed improvement of their symptoms changed the status of their MEBO/PATM condition from "active" to "remission/regression", their samples were grouped in two subgroups (38+33+23+6 = 84+16) Units analyzed represents samples submitted, 233 total.

Arm/Group Title	Subjects With Active MEBO	Subjects With Active PATM	Subjects in Regression or Remission	Non MEBO/PATM Cohort
Arm/Group Description	Individuals experiencing uncontrollable episodes of malodor that did not self-diagnose PATM	Individuals experiencing uncontrollable episodes of PATM with or without malodor	Individuals self-reporting remission or regression of MEBO/PATM (lessening of the severity or disappearance of the symptoms)	individuals that never experienced MEBO/PATM episodes
Measure Participants	38	33	23	6
Measure gut microbiome samples	97	85	35	16
Mean (95% Confidence Interval) [unitless]	1.7	1.6	1.7	1.9

Adverse Events

Time Frame	participants were observed for one year
Arm/Group Title	Study Participants
Arm/Group Description	The cohort is individuals who consented to submit stool samples, including those who experienced symptoms of idiopathic malodor or PATM ("people allergic to me" condition) and received the support-group intervention.
All Cause Mortality
	Study Participants
	Affected / at Risk (%)	# Events
Total	0/125 (0%)
Serious Adverse Events
	Study Participants
	Affected / at Risk (%)	# Events
Total	0/125 (0%)
Other (Not Including Serious) Adverse Events
	Study Participants
	Affected / at Risk (%)	# Events
Total	0/125 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.