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This trial is being completed to learn about how Aquamin® affects gastrointestinal permeability, or the control of material passing from inside the gastrointestinal tract through the gut wall into the rest of the body, in people with ulcerative colitis (UC), Irritable Bowel Syndrome with diarrhea (IBS-D), and in healthy individuals.
This is a sub-study to the ongoing clinical trial entitled: Aquamin®, a multi-mineral natural product from red marine algae, as an adjuvant intervention for mild ulcerative colitis and ulcerative colitis in remission (HUM00156676) NCT# NCT03869905.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Aquamin® | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Aquamin | Drug | Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Lactulose:Mannitol Ratio in Urine by Comparing Values at 90-days (Post-intervention) to Baseline (Pre-intervention) Levels. | Baseline (pre-intervention), 90 days (post-intervention) | |
| Mannitol Levels in Urine Samples | Though lactulose measurements could not be taken from urine samples, the study team was able to measure mannitol levels in those samples. Higher mannitol levels in urine indicate higher levels of permeability. Participants provided baseline urine samples before drinking a mixture of lactulose/mannitol powder and water. Additional samples were then provided within 0-2 hour window, within a 2-8 hour window, and within an 8-24 hour window of drinking the lactulose/mannitol solution. This test was performed on "day 0" (prior to the participant beginning Aquamin treatment) and day 90 (after the participant had been taking Aquamin for 90 days). | 90 days |
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Inclusion Criteria for UC participants:
If cessation of menses is within 12 months, then the participant will be treated as pre-menopausal and a pregnancy test will be performed.
Inclusion Criteria for Healthy participants:
Inclusion Criteria for participants with IBS-D:
Exclusion Criteria For UC participants:
Crohn's disease, Any stomach or intestinal bleeding disorders (gastrointestinal bleeding from gastric or duodenal ulcers, or gastrin secreting tumors) or active gastric/duodenal ulcers - peptic ulcer disease (without bleeding in last 3 months).
Exclusion Criteria For Healthy participants:
Kidney disease, including kidney "stones" or hypercalcemia, Crohn's disease, Neurologic disease, other inflammatory bowel disease, any stomach or intestinal bleeding disorders (gastrointestinal bleeding from gastric or duodenal ulcers, or gastrin secreting tumors) or active gastric/duodenal ulcers - peptic ulcer disease (without bleeding in last 3 months).
Exclusion Criteria for participants with IBS-D:
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| Name | Affiliation | Role |
|---|---|---|
| James Varani | University of Michigan | Principal Investigator |
| Muhammad N Aslam | University of Michigan | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Michigan Hospital | Ann Arbor | Michigan | 48109 | United States |
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Recruitment for the IBS-D arm was significantly slower than anticipated. 4 participants were consented. 2 participants withdrew prior to taking the study drug. Of the 2 remaining participants in this arm, only 1 submitted evaluable data before the study closed. This participant's data and, therefore, the IBS-D arm's data was not included in the data analysis for any outcome measure.
Also, 2 participants in the healthy arm were determined to be ineligible due to exclusion criteria.
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| ID | Title | Description |
|---|---|---|
| FG000 | Aquamin® - Healthy Subjects | Participants in this arm were healthy participants without Ulcerative Colitis Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| FG001 | Aquamin® - Subjects With Ulcerative Colitis | Participants in this arm were Ulcerative Colitis patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| FG002 | Aquamin® - Subjects With IBS-D | Participants in this arm were Irritable Bowel Syndrome - D patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
One participant in the IBS-D arm did not submit demographic data.
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| ID | Title | Description |
|---|---|---|
| BG000 | Aquamin® - Healthy Subjects | Participants in this arm were healthy participants without Ulcerative Colitis Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in the Lactulose:Mannitol Ratio in Urine by Comparing Values at 90-days (Post-intervention) to Baseline (Pre-intervention) Levels. | Lactulose:mannitol ratio could not be calculated because lactulose measures could not be generated from the urine samples. The study took place over the COVID-19 pandemic, during which the company that manufactured the ELISA assays for lactulose measurement closed and ceased production. Alternatives to these assays were sought and tested, but none were found to be accurate. Therefore, reliable lactulose measurements could not be taken from urine samples. No data will be analyzed in the future. | Posted | Baseline (pre-intervention), 90 days (post-intervention) |
|
Up to 95 days
Data is shown for participants who enrolled and were administered at least the baseline mannitol/lactulose solution, regardless of whether or not they continued in the study to take the study drug.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Aquamin® - Healthy Subjects | Participants in this arm were healthy participants without Ulcerative Colitis Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bone graft surgery for dental implant | Surgical and medical procedures | Systematic Assessment | Scheduled prior to participant enrollment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. James Varani | University of Michigan Medical School | 734-615-0298 | jvarani@umich.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 23, 2024 | Mar 26, 2026 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| C572820 | Aquamin |
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|
| Aquamin® - Subjects With Ulcerative Colitis |
Participants in this arm were Ulcerative Colitis patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| BG002 | Aquamin® - Subjects With IBS-D | Participants in this arm were Irritable Bowel Syndrome - D patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| OG001 | Aquamin® - Subjects With Ulcerative Colitis | Participants in this arm were Ulcerative Colitis patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). |
|
| Primary | Mannitol Levels in Urine Samples | Though lactulose measurements could not be taken from urine samples, the study team was able to measure mannitol levels in those samples. Higher mannitol levels in urine indicate higher levels of permeability. Participants provided baseline urine samples before drinking a mixture of lactulose/mannitol powder and water. Additional samples were then provided within 0-2 hour window, within a 2-8 hour window, and within an 8-24 hour window of drinking the lactulose/mannitol solution. This test was performed on "day 0" (prior to the participant beginning Aquamin treatment) and day 90 (after the participant had been taking Aquamin for 90 days). | Data were analyzed from samples that were submitted by participants in the Healthy Subjects and UC arms. Some participants did not submit samples for any time period. One participant did not generate a sample for a single time window. Data from the IBS-D arm was not analyzed due to a lack of usable data. | Posted | Mean | Standard Deviation | mgs | 90 days |
|
|
|
|
| 0 |
| 14 |
| 0 |
| 14 |
| 7 |
| 14 |
| EG001 | Aquamin® - Subjects With Ulcerative Colitis | Participants in this arm were Ulcerative Colitis patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). | 0 | 12 | 0 | 12 | 6 | 12 |
| EG002 | Aquamin® - Subjects With IBS-D | Participants in this arm were IBS-D patients Aquamin: Participants will take a 90-day supply of Aquamin®, 4 capsules per day; 2 to be taken in the morning and 2 in the evening (containing approximately 800 mg calcium/day). | 0 | 3 | 0 | 3 | 3 | 3 |
|
| Lactulose/Mannitol related migraine headache | General disorders | Systematic Assessment | Migraine headache experienced after consumption of mannitol solution, prior to the initial administration of the study drug. |
|
| Lactulose/Mannitol related diarrhea | Gastrointestinal disorders | Systematic Assessment | Diarrhea experienced after consumption of mannitol solution, prior to the initial administration of the study drug. |
|
| Nausea | Gastrointestinal disorders | Systematic Assessment |
|
| Flatulence | Gastrointestinal disorders | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Chest Pain | General disorders | Systematic Assessment | Chest pain from undiagnosed source |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Hepatobiliary disorders | Hepatobiliary disorders | Systematic Assessment | Mild elevated LFTS |
|
| Gilberts disease | Hepatobiliary disorders | Systematic Assessment |
|
| Abdominal discomfort with bloating | Gastrointestinal disorders | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Systematic Assessment |
|
| Fatigue | General disorders | Systematic Assessment |
|
| Joint pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Minor blood in stool with lower abdominal ache | Gastrointestinal disorders | Systematic Assessment |
|
| OCD-related distress | Psychiatric disorders | Systematic Assessment | OCD-related distress triggered by performing urine collection |
|
| Tonsil stones | General disorders | Systematic Assessment |
|
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| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| Baseline - Day 90 |
|
|
| 0-2 hour window - Day 0 |
|
|
| 0-2 hour window - Day 90 |
|
|
| 2-8 hour window - Day 0 |
|
|
| 2-8 hour window - Day 90 |
|
|
| 8-24 hour window - Day 0 |
|
|
| 8-24 hour window - Day 90 |
|
|
This statistical analysis compares the healthy subject cohort at Days 0 and 90. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (2-8 h).
| t-test, 2 sided |
| 0.809 |
Threshold value is <0.05 |
| Superiority |
| This statistical analysis compares the healthy subject cohort at Days 0 and 90. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (8-24 h). | t-test, 2 sided | 0.881 | Threshold value is <0.05. | Superiority |
| This statistical analysis compares the UC subject cohort at Days 0 and 90. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (0-2 h). | t-test, 2 sided | 0.015 | Threshold value is <0.05 | Superiority |
| This statistical analysis compares the UC subject cohort at Days 0 and 90. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (2-8 h). | t-test, 2 sided | 0.126 | Threshold value is <0.05 | Superiority |
| This statistical analysis compares the UC subject cohort at Days 0 and 90. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (8-24 h). | t-test, 2 sided | 0.546 | Threshold value is <0.05 | Superiority |
| This statistical analysis compares the healthy subject cohort and UC subject cohort. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (0-2 h) on Day 0. | t-test, 2 sided | 0.006 | Threshold value is <0.05 | Superiority |
| This statistical analysis compares the healthy subject cohort and UC subject cohort. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (2-8 h) on Day 0. | t-test, 2 sided | 0.123 | Threshold value is <0.05 | Superiority |
| This statistical analysis compares the healthy subject cohort and UC subject cohort. Difference values were calculated in urinary mannitol excretion across the individual urine collection intervals (8-24 h) on Day 0. | t-test, 2 sided | 0.908 | Threshold value is <0.05 | Superiority |