Safety Issues
Conditions
Brief summary
The aim of the present study was to determine whether oral dosing, up to 9 grams/day, of porous silica administered as a food additive can be used safely in normal weight and obese male humans, without significant side effects on gastrointestinal function, bowel emptying habits, and biomarkers.
Detailed description
This single blinded safety study will consist of two study arms and include 10 males each (18-35 years). One arm will include participants with normal weight and one with obesity. After a placebo run-in period, all subjects will be given porous silica three times daily, with increasing dose up to 9 grams/day (Phase 1). Subjects with obesity continued the study with highest dose for additional 10 weeks (Phase 2). The participants will have weekly contacts during with the representative for the study (PI or other research staff). Clinical examinations, and blood sampling will be performed day 1, 7, 14, and 21. Faeces and morning urinary sampling day 1, and 21. Information regarding eating habits, sleep patterns, living conditions and gastrointestinal health were obtained from written forms and orally. If gastrointestinal adverse events would occur after increased dosage, the study staff will adapt the dosage protocol to facilitate adherence.
Interventions
DIETARY_SUPPLEMENTPorous silica
The particle is rod shaped and approximately 1-3 x 0.4-0.5 micrometers with pore sizes in the range of 70-130 Ångström or 7-13 nanometer.
DIETARY_SUPPLEMENTPlacebo (microcrystalline cellulose)
All participants starts with five days placebo run in period
Sponsors
Sigrid Therapeutics AB, Sweden
Stockholm University
Karolinska Institutet
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
Group - Normal weight subjects * Age 18-35 * BMI 20-25 Group - Subject with obesity * Age 18-35 * BMI 30-45
Exclusion criteria
* Chronic somatic diseases that may affect metabolic and/or intestinal function (e.g. diabetes, hypertension, dyslipidemia, Irritable Bowel Disease, gluten intolerance, pancreatic dysfunction, other causes of malabsorption, neoplastic disease,) * Allergies with previous anaphylactic reactions * Previous abdominal surgery * Current or history of eating disorders * Extreme or unusual diets such as Low Carb High Fat and vegetarian diets for the last year * Psychiatric disorders (e.g. schizophrenia, and other diagnoses that may influence compliance) * Drug or alcohol abuse * Continuous oral pharmacological treatment and other types of pharmacological treatment that may influence the study * Other conditions which the investigator considers could negatively affect the outcome of the study or study compliance
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | From start of intervention up to 12 weeks | According to MedDRA SOC. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in glucose metabolism | From start of intervention up to 12 weeks | Fasting glucose, insulin and hemoglobin A1c in blood |
| Number of participants with affected gastrointestinal function | From start of intervention up to 12 weeks | Evaluates by 5 graded questions of gastrointestinal habits and discomfort |
| Presence of fecal abnormalities | From start of intervention up to 12 weeks | Tests of Hemoglobin, calprotectin and elastase in feces |
| Change in nutrition status | From start of intervention up to 12 weeks | Vitamin and trace elements levels measured in blood |
| Change in lipid profile | From start of intervention up to 12 weeks | Triglycerides, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol in blood |
| Change in liver status | From start of intervention up to 12 weeks | Alanine aminotransferase and aspartate aminotransferase in blood |
| Change in renal status measured by creatinine | From start of intervention up to 12 weeks | Creatinine in blood |
| Change in renal status measured by glomerular filtration rate | From start of intervention up to 12 weeks | Glomerular filtration rate in blood |
| Change in renal status measured by cystatin C | From start of intervention up to 12 weeks | Cystatin C in blood |
| Change in concentration of silica | From start of intervention up to 12 weeks | Urine sample |
| Change in systemic inflammation status | From start of intervention up to 12 weeks | C-reactive protein in blood |
| Change in blood pressure | From start of intervention up to 12 weeks | Diastolic and systolic blood pressure |
| Body weight | From start of intervention up to 12 weeks | Weight (kg) |
Outcome results
None listed