PMA-Zeolite-Clinoptilolite Effects in Crohn Disease

Evaluation of PMA-Zeolite-Clinoptilolite Effects on the Dysbiosis and Inflammation in Patients With Uncontrolled Crohn Disease

This pilot study aims to evaluate the safety and efficacy of PMA-zeolite when used in patients with uncontrolled CD (Crohn´s disease). The effect of the PMA-zeolite will be compared between a control-group (healthy volunteers) receiving either PMA-zeolite or placebo and the test-group (suffering from uncontrolled CD) and receiving either PMA-zeolite or placebo. In addition, this pilot-study should furthermore provide indications for the effect-size in order to estimate an effect for an eventual further human trial.

Study Overview

• Status: Unknown
• Conditions: Crohn Disease
• Intervention / Treatment: Device: cellulose; Device: PMA-zeolite

Detailed Description

Background of the study Crohn´s disease (CD) is a chronic progressive destructive disease. Approximately one-fifth of adult and paediatric patients already have evidence of a structuring or penetrating intestinal complications at diagnosis. Despite decades of research, the aetiology of CD remains unknown. Disease treatments include a variety of approaches like dietary changes and immunosuppressive anti-TNFa antibodies as well as ancillary antibiotic therapy. Another interesting and promising approach in this context might be the supplementation of the certified medical device PMA-(Panaceo micro activation)-zeolite (a specific natural zeolite-clinoptilolite) due to its properties documented through many studies. In particular, the promising clinical results from a randomized controlled trial (RCT) with PMA-zeolite need to be highlighted. The strengthening/ supporting of the intestinal wall integrity in healthy subjects suffering from intestinal problems was measured in this RCT and is claimed as intended main action of the PMA-zeolite. Based on these results the application of PMA-zeolite is an interesting and promising approach in patients with uncontrolled CD.

Hypothesis In the present trial, it is being tested if supplementing PMA-zeolite can lead to an improvement of the defined markers and parameters (reduction of local and systemic inflammation, changes of the microbiota in the gut, positive detoxifying effect and general improvement of quality of life) in patients with uncontrolled CD compared to a healthy test-group.

Aims This pilot study aims to evaluate the safety and efficacy of PMA-zeolite when used in patients with uncontrolled CD. The effect of the PMA-zeolite will be compared between a control-group (healthy volunteers) receiving either PMA-zeolite or placebo and the test-group (suffering from uncontrolled CD) and receiving either PMA-zeolite or placebo. In addition, this pilot-study should furthermore provide indications for the effect-size in order to estimate an effect for an eventual further human trial.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Krešimir Pavelić, Phd, M.D.; Phone Number: + 385 98 247164; Email: pavelic@unipu.hr
• Study Contact Backup: Name: Sandra Kraljević Pavelić, Phd; Phone Number: + 385 51 584569; Email: sandrakp@uniri.hr

Study Locations

• Slovenia
  • Ljubljana, Slovenia, 1000
    • Recruiting
    • University Clinical Centre Ljubljana
    • Contact: Joško Osredkar, Phd., M.D.; Phone Number: + 386 1 522 24 37; Email: josko.osredkar@kclj.si
  • Maribor, Slovenia, 2000
    • Recruiting
    • Medical Thermal Centre Fontana
    • Contact: Željko Perdija, M.D.; Phone Number: + 386 2 23 44 102; Email: zdravstvo@termemb.si
  • Slovenj Gradec, Slovenia, 2380
    • Recruiting
    • Slovenj Gradec General Hospital
    • Contact: Željko Perdija, M.D.; Phone Number: +386 2 882 34 00; Email: zeljko.perdija@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy volunteers (at least 18 years old) for first two groups (A,B), homogenous starting group in age (30-60Y) and sex (m/f )

  o The health-status will be confirmed through anamnesis.

• Groups C and D will include patients with confirmed Crohn's disease that are treated with standard therapy and despite of treatment do not achieve the appropriate disease remission. Patients with the intermediate type of disease will be also included in groups C and D.

  • Diagnosis has to be confirmed with a biopsy of the intestine and histological exam.
  • Degree of disease will be assessed by Harvey-Bradshaw Index (HBI). For evaluation of quality BDQ questionnaire will be used. For the assessment of disease activity ordinary laboratory measurements will be performed (CBC, basic biochemical parameters, CRP), and calprotectin from chairs. Colonoscopy must be done in the last six months prior to inclusion of patients in the research protocol. Gastrointestinal system degree of impairment will not have influence on inclusion criteria and patients with histological intermediate type of disease will be included as well.
• Signed informed consent as per usual recommendations in vigour in the Republic of Slovenia.

Exclusion Criteria:

• Signs of acute bacterial infection (fever >38°C, nausea, vomiting).
• Other chronic disease (cancer, renal disease, neuro-degenerative, metabolic disorders, diabetic).
• Pregnancy or breastfeeding
• Food supplements** **NOTE: Food supplements: if taken regularly this should be continued also during the study and documented - otherwise a wash - out - phase would be necessary

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control group + cellulose (Group A); healthy subjects (control group) receive placebo (cellulose) as powder	Device: cellulose; The subjects of group A and group C receive boxes containing placebo for supplementation for a total of 12 weeks.
Active Comparator: Control group + PMA-zeolite(Group B); healthy subjects (control group) receive PMA-zeolite as powder	Device: PMA-zeolite; The subjects of group B and group D receive boxes containing PMA-zeolite for supplementation for a total of 12 weeks.
Placebo Comparator: UCD-group + Cellulose (Group C); subjects with uncontrolled Crohn disease (UCD group) receive placebo (cellulose) as powder	Device: cellulose; The subjects of group A and group C receive boxes containing placebo for supplementation for a total of 12 weeks.
Active Comparator: UCD-group + PMA-zeolite (Group D); subjects with uncontrolled Crohn disease receive PMA-zeolite as powder	Device: PMA-zeolite; The subjects of group B and group D receive boxes containing PMA-zeolite for supplementation for a total of 12 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Zonulin concentration in stool (ng/ml)	As the intestinal wall permeability is linked to several conditions, such as the Crohn Disease it is hypothesized that a change of Zonulin (biomarker for permeability of intestinal wall) is detectable with/without supplementation of the study-substance. Measurement: stool stool sample (by ELISA kit) Standard Value for Zonulin: < 55 ng/ml .	0(baseline) and after 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bacterial diversity in the marbus crohn patients	bactieria of assessment: Lactobacillus, Escherichia, bifidobacteria Measurement: stool sample (16S RNA sequencing on stool sampling)	0(baseline) and after 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of blood parameters	Blood samples for measurement of definied parameters: Ni: 0,6-3,8 µg/L; Al: < 7,0 µg/L; Na: 3100,0 - 3350,0 mg/L; K: 140,0 - 200,0 mg/L; Mg: 17,0-23,0 mg/L; Ca: 89,0-101,0 mg/L; Se: 70,0-150,0 µg/L; Zn: 660,0-1100,0 µg/L; Cu: 750,0-1450,0 µg/L; Fe: M: 550,0-1600,0 µg/L; F: 400,0-1550,0 µg/L DAO (Standard Value > 10 U/ml ), ammonia - µmol/l,histamine (ng/ml), Measurement of sedimentation, blood count, electrolytes, urea, liver-parameters, creatinine and other	0(baseline) and after 12 weeks
Rate of Safety and tolerability	Rate of tolerability and safety levels of minerals and metals	0(baseline) and after 12 weeks

Collaborators and Investigators

• Sponsor: Ciim Plus, d.o.o.
• Collaborators: University of Rijeka
• Investigators: Principal Investigator: Krešimir Pavelić, PhD, M.D., Juraj Dobrila University of Pula

Publications and helpful links

General Publications

• Kraljevic Pavelic S, Saftic Martinovic L, Simovic Medica J, Zuvic M, Perdija Z, Krpan D, Eisenwagen S, Orct T, Pavelic K. Clinical Evaluation of a Defined Zeolite-Clinoptilolite Supplementation Effect on the Selected Blood Parameters of Patients. Front Med (Lausanne). 2022 May 27;9:851782. doi: 10.3389/fmed.2022.851782. eCollection 2022.

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2018
• Primary Completion (Actual): November 28, 2019
• Study Completion (Anticipated): May 15, 2020

Study Registration Dates

• First Submitted: May 4, 2018
• First Submitted That Met QC Criteria: April 28, 2020
• First Posted (Actual): May 1, 2020

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Inflammatory Bowel Diseases; Crohn Disease
• Other Study ID Numbers: crohn-disease ver. 1.3_17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No