Dietary Soy Isoflavones In Chronic Pancreatitis

• Sponsor: Ohio State University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02577640
• Collaborator: (none)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 24
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Dietary Soy Isoflavones in Chronic Pancreatitis: Investigating the Anti-inflammatory Effects of Food Innovation Science on Gastrointestinal Disease

Condition or Disease	Intervention/Treatment	Phase
Chronic Pancreatitis	Dietary Supplement: Soy bread	N/A

Detailed Description

Management of pancreatic disorders imparts a major burden on healthcare costs, estimated at over 3 billion dollars annually. Chronic pancreatitis is characterized by chronic inflammation and progressive scarring, leading to abdominal pain, irreversible damage to the pancreas and the loss of both exocrine and endocrine function. Additionally, chronic pancreatic inflammation is a risk factor for pancreas cancer. There are no current treatments to modify the natural history of this disorder. Thus, identifying novel therapeutic options for this disease represents a high priority, and could fill an unmet medical need to improve quality of life, reduce risk of malignant transformation, and limit exorbitant medical costs associated with patient care. The investigators have assembled a multi-disciplinary research team to pursue an alternative, non-pharmacologic approach to limiting inflammatory cascades in (Chronic Pancreatitis) CP patients. They will assess compliance, toxicity and measure the changes in pro-inflammatory cytokine expression from a soy based dietary bread product using a classic 3+3 dose escalation study design in subjects with chronic pancreatitis.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dietary Soy Isoflavones In Chronic Pancreatitis
• Study Start Date: Jul 1, 2015
• Actual Primary Completion Date: Jul 1, 2017
• Actual Study Completion Date: Jul 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation (DE) Phase Here a traditional 3+3 design will be used to determine the compliance, tolerability and dose limiting toxicities in this unique patient population. Dose escalation with soy bread will be continued until dose-limiting toxicities are observed in >33% of the participants or the daily target dose of 4 slices of bread [132 mg soy isoflavone] is reached.	Dietary Supplement: Soy bread; Soy breads will be produced using a sponge-dough process. Finished dough will be formed, panned, and proofed in proofing cabinet (~95% RH) at 40ºC for 60 minutes. Proofed loaves will be baked for 50 minutes at 150ºC in a convection oven (jet air oven, model: JA14, Doyon, Liniere, Quebec, Canada). Breads will be considered done at an internal temperature of 95 ± 5ºC.; Other Names: Soy Isoflavones
Experimental: Maximum Tolerated Dose (MTD) Phase After the Phase I study has been completed, an additional 10 chronic pancreatitis patients will be treated at the best tolerated dose of soy bread for 4 weeks to further verify safety and toxicity.	Dietary Supplement: Soy bread; Soy breads will be produced using a sponge-dough process. Finished dough will be formed, panned, and proofed in proofing cabinet (~95% RH) at 40ºC for 60 minutes. Proofed loaves will be baked for 50 minutes at 150ºC in a convection oven (jet air oven, model: JA14, Doyon, Liniere, Quebec, Canada). Breads will be considered done at an internal temperature of 95 ± 5ºC.; Other Names: Soy Isoflavones

Outcome Measures

Primary Outcome Measures

1. Dose Limiting Toxicities [1 (dose escalation groups) or 4 (maximally tolerated dose) weeks]

   Participants were evaluated for the development of bothersome symptoms that prevented them from being able to complete the recommended intervention course. Counts represent number of subjects who developed a symptom that prevented the ability to complete the dose/study period.

Secondary Outcome Measures

1. Pro-inflammatory Cytokines [1 (dose escalation group) or 4 weeks (maximally tolerated subject)]

   Changes in the serum were assessed for TNF-alpha prior to and following introduction of soy bread

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Diagnosis of chronic pancreatitis by fulfilling one of the following clinical scenarios:

2. Presence of pancreatic calcifications

3. Suggestive for chronic pancreatitis - consistent EUS criteria or at least 3 abnormal side branches on pancreatic duct imaging

4. Indeterminate EUS findings for chronic pancreatitis with evidence of exocrine pancreatic insufficiency (EPI)

5. Age ≥18 years

Exclusion Criteria:

1. Inability to provide written consent

2. Inability to comply with the study protocol

3. Soy allergy

4. Pancreatic cancer

5. History of prior pancreatic surgery (this does not include endoscopic therapies)

6. Comorbid diseases characterized by a chronic inflammatory state, including, but not limited to rheumatologic diseases, chronic kidney disease, extra-pancreatic malignancy

7. Pregnancy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Philip Hart	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Ohio State University

Investigators

• Principal Investigator: Philip Hart, MD, The Ohio State Wexner Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 5, 2013

More Information

Publications

• Ahn-Jarvis J, Lombardo E, Cruz-Monserrate Z, Badi N, Crowe O, Kaul S, Komar H, Krishna SG, Lesinski GB, Mace TA, Ramsey ML, Roberts K, Stinehart K, Traczek M, Conwell DL, Vodovotz Y, Hart PA. Reduction of inflammation in chronic pancreatitis using a soy bread intervention: A feasibility study. Pancreatology. 2020 Jul;20(5):852-859. doi: 10.1016/j.pan.2020.04.018. Epub 2020 Jun 6.

• Responsible Party: Philip Hart, Assistant Professor-Clinical, Ohio State University
• ClinicalTrials.gov Identifier: NCT02577640
• Other Study ID Numbers: 2014H0226
• First Posted: Oct 16, 2015
• Last Update Posted: Nov 12, 2021
• Last Verified: Oct 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Pancreatitis; Pancreatitis, Chronic

Study Results

Participant Flow

Arm/Group Title	Dose Escalation Group 1	Dose Escalation Group 2	Dose Escalation Group 3	Maximally Tolerated Dose
Arm/Group Description	DE group at 1 slice of bread per day.	DE group at 2 slices of bread per day	DE group at 3 slices of bread per day	maximally tolerated dose of bread for 4 week period
Period Title: Dose Escalation Group 1
STARTED	4	0	0	0
COMPLETED	3	0	0	0
NOT COMPLETED	1	0	0	0
Period Title: Dose Escalation Group 1
STARTED	0	3	0	0
COMPLETED	0	3	0	0
NOT COMPLETED	0	0	0	0
Period Title: Dose Escalation Group 1
STARTED	0	0	3	0
COMPLETED	0	0	3	0
NOT COMPLETED	0	0	0	0
Period Title: Dose Escalation Group 1
STARTED	0	0	0	1
COMPLETED	0	0	0	1
NOT COMPLETED	0	0	0	0

Baseline Characteristics

Arm/Group Title	Dose Escalation Group 1	Dose Escalation Group 2	Dose Escalation Group 3	Maximally Tolerated Dose	Total
Arm/Group Description	1 slice bread per day for 1 week	2 slices bread per day for 1 week	3 slices bread per day for 1 week	maximally tolerated dose for 4 weeks	Total of all reporting groups
Overall Participants	4	3	1	1	9
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 50%	0 0%	1 100%	0 0%	3 33.3%
>=65 years	2 50%	3 100%	0 0%	1 100%	6 66.7%
Sex: Female, Male (Count of Participants)
Female	1 25%	1 33.3%	0 0%	0 0%	2 22.2%
Male	3 75%	2 66.7%	1 100%	1 100%	7 77.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 50%	1 33.3%	0 0%	0 0%	3 33.3%
White	2 50%	2 66.7%	1 100%	1 100%	6 66.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Dose Limiting Toxicities
Description	Participants were evaluated for the development of bothersome symptoms that prevented them from being able to complete the recommended intervention course. Counts represent number of subjects who developed a symptom that prevented the ability to complete the dose/study period.
Time Frame	1 (dose escalation groups) or 4 (maximally tolerated dose) weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Dose Escalation Group 1	Dose Escalation Group 2	Dose Escalation Group 3	Maximally Tolerated Dose Group
Arm/Group Description	1 slice bread per day	2 slices per day	3 slices per day	maximally tolerated dose (3 slices/day)
Measure Participants	3	3	3	1
Count of Participants [Participants]	0 0%	0 0%	0 0%	0 0%

2. Secondary Outcome

Title	Pro-inflammatory Cytokines
Description	Changes in the serum were assessed for TNF-alpha prior to and following introduction of soy bread
Time Frame	1 (dose escalation group) or 4 weeks (maximally tolerated subject)

Outcome Measure Data

Analysis Population Description

For the purposes of analyzing the secondary outcomes all subjects completing any of the dose escalation groups were combined.

Arm/Group Title	Dose Escalation (DE) Phase	Maximum Tolerated Dose (MTD) Phase
Arm/Group Description	Data for each of the 3 doses were examined collectively.	Actual data for subjects who completed MTD phase over 4 weeks.
Measure Participants	9	1
Day 0 value of TNF-alpha	2.67 (0.72)	7.0 (0)
Day 7 value of TNF-alpha	2.38 (0.56)	7.2 (0)

Adverse Events

Time Frame	up to 4 weeks
Arm/Group Title	Dose Escalation Group 1		Dose Escalation Group 2		Dose Escalation Group 3		Maximally Tolerated Dose
Arm/Group Description	1 slice per day		2 slices per day		3 slices per day		an extended exposure to the maximally tolerated dose of 3 slices per day.
All Cause Mortality
	Dose Escalation Group 1		Dose Escalation Group 2		Dose Escalation Group 3		Maximally Tolerated Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/1 (0%)
Serious Adverse Events
	Dose Escalation Group 1		Dose Escalation Group 2		Dose Escalation Group 3		Maximally Tolerated Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	Dose Escalation Group 1		Dose Escalation Group 2		Dose Escalation Group 3		Maximally Tolerated Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/3 (0%)		0/3 (0%)		0/3 (0%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.