Safety and efficacy of purified clinoptilolite-tuff treatment in patients with irritable bowel syndrome with diarrhea: Randomized controlled trial

Table 1 Demographic characteristics and concomitant medications at baseline

Characteristics and medications		G-PUR®, n = 14	Placebo, n = 16	Total, n = 30
Age, yr		34 (range: 24–61)	35 (range: 20–73)	34 (range: 20–73)
Sex	Male	5 (35%)	4 (25%)	9 (30%)
	Female	9 (64%)	12 (75%)	21 (70%)
Duration of IBS symptoms, yr		12 (IQR: 6–19)	9 (IQR: 6–21)	11 (IQR: 6–20)
Duration of IBS diagnosis, yr		8 (IQR: 3–11)	2 (IQR: 1–11)	4 (IQR: 1–11)
BMI, kg/m2		21 (IQR: 20–25)	24 (IQR: 21–26)	23 (IQR: 20–26)
Smoking status	Non-smoker	9 (64%)	11 (69%)	20 (67%)
	Ex-smoker	3 (21%)	4 (25%)	7 (23%)
	Smoker	2 (14%)	1 (6%)	3 (10%)
Concomitant medications
Any concomitant medication		12 (86%)	15 (94%)	27 (90%)
Analgesics		2 (14%)	8 (50%)	10 (33%)
Drugs for functional gastrointestinal disorders		4 (29%)	5 (31%)	9 (30%)
Selective serotonin reuptake inhibitors		4 (29%)	4 (25%)	8 (27%)
Systemic antihistamines		5 (36%)	1 (6%)	6 (20%)
Loperamide PRN		2 (14%)	2 (13%)	4 (13%)
Antacids		1 (7%)	1 (6%)	2 (7%)
Hypnotics, sedatives, antipsychotics		0 (0%)	2 (13%)	2 (7%)
Tonics		1 (7%)	1 (6%)	2 (7%)
Systemic antibiotics1		0 (0%)	1 (6%)	1 (3%)
Digestives, incl. enzymes		1 (7%)	0 (0%)	1 (3%)
Drugs for constipation		1 (7%)	0 (0%)	1 (3%)

¹Macrolides, lincosamides and streptogramins.

BMI: Body mass index; IBS: Irritable bowel syndrome; IQR: Interquartile range; PRN: Pro re nata (as necessary).

Table 2 Medical history at baseline

System organ class	G-PUR®, n = 14	Placebo, n = 16	Total, n = 30
MedDRA term
Immune system disorders	10 (71%)	6 (38%)	16 (53%)
Seasonal allergy	7 (50%)	3 (19%)	10 (33%)
Drug hypersensitivity	2 (14%)	2 (13%)	4 (13%)
Allergy to animal	1 (7%)	1 (6%)	2 (7%)
Allergy to plants	2 (14%)	0 (0%)	2 (7%)
Food allergy	1 (7%)	1 (6%)	2 (7%)
Mite allergy	1 (7%)	1 (6%)	2 (7%)
Perfume sensitivity	1 (7%)	0 (0%)	1 (3%)
Metabolism and nutrition disorders	3 (21%)	7 (44%)	10 (33%)
Vitamin D deficiency	1 (7%)	5 (31%)	6 (20%)
Lactose intolerance	2 (14%)	1 (6%)	3 (10%)
Fructose intolerance	1 (7%)	1 (6%)	2 (7%)
Folate deficiency	0 (0%)	1 (6%)	1 (3%)
Food intolerance	0 (0%)	1 (6%)	1 (3%)
Hypercholesterolemia	0 (0%)	1 (6%)	1 (3%)
Psychiatric disorders	3 (21%)	5 (31%)	8 (27%)
Depression	2 (14%)	2 (13%)	4 (13%)
Anxiety disorder	0 (0%)	3 (19%)	3 (10%)
Burnout syndrome	1 (7%)	0 (0%)	1 (3%)
Sleep disorder	1 (7%)	0 (0%)	1 (3%)
Gastrointestinal disorders	1 (7%)	5 (31%)	6 (20%)
Gastritis	0 (0%)	3 (19%)	3 (10%)
Gastroesophageal reflux disease	1 (7%)	1 (6%)	2 (7%)
Hiatus hernia	0 (0%)	1 (6%)	1 (3%)
Nausea	0 (0%)	1 (6%)	1 (3%)

Data are presented for patients randomized to receive G-PUR^® or placebo, given as absolute numbers and percent of group. Headings represent the standard nomenclature and structure from the Medical Dictionary for Regulatory Activities. MedDRA: Medical Dictionary for Regulatory Activities.

Table 3 Study outcome variables at week 12 of treatment with G-PUR^® or placebo

Outcome variable		G-PUR®, n = 14	Placebo, n = 16	RD/MD (95%CI)	Odds ratio (95%CI)	P value
SGA of Relief responders, end of study1		3 (21%)	4 (25%)	0.04 (-0.28-0.38)	0.82 (0.18-3.73)	1.0000
Abdominal pain responders2		13 (93%)	13 (81%)	0.12 (-0.20-0.40)	3 (0.39-41.55)	0.6015
Daily abdominal pain reduction3		94 (IQR: 81-100)	83 (IQR: 65-92)	-14.9 (-31.87-2.07)	N/A	0.0353
Proportion of BSFS 50% responders		7 (50%)	5 (31%)	0.19 (-0.19-0.51)	2.2 (0.55-11.05)	0.4572
Proportion of BSFS 30% responders		10 (71%)	7 (44%)	0.28 (-0.11-0.58)	3.21 (0.76-12.03)	0.1590
Combined abdominal pain and BSFS 50% response		6 (43%)	4 (25%)	0.18 (-0.19-0.50)	2.25 (0.49-8.68)	0.4421
Decrease in d with diarrhea per week		2.4	0.3	N/A	N/A	0.4176
IBS-SSS		-90 (IQR: -170 to -40)	-55 (IQR: -100 to -10)	31.6 (-42.25-105.5)	N/A	0.3950
SF-12		53 (IQR: 50-55)	49 (IQR: 42-51)	-5.40 (-9.15 to -1.65)	N/A	0.0127
PSQ absolute change	Total	-7 (IQR: -28-0)	5 (IQR: -5-12)	11.0 (-2.65-24.65)	N/A	0.0843
	Tension	-20 (IQR: -40-0)	-3 (IQR: -13-13)	16.2 (0.7-31.7)	N/A	0.0399
	Joy	13 (IQR: -7-20)	-10 (IQR: -20-0)	-10.4 (-25.3-4.5)	N/A	0.1176
	Demands	-7 (IQR: -33-13)	10 (IQR: -7-20)	14.3 (-5.35-33.95)	N/A	0.1795
	Worries	0 (IQR: -13-0)	0 (IQR: -7-13)	3.2 (-11.56-17.96)	N/A	0.5587

¹Subject’s Global Assessment (SGA) of Relief response assessment was based on the last four post-randomization SGAs, or if fewer than four post-randomization SGAs were available, then all post-randomization SGAs were used. Patients were considered responders if they answered ‘considerably relieved’ or ‘completely relieved’ at least 50% of the time or at least ‘somewhat relieved’ 100% of the time.

²Abdominal pain response was defined as an at least 30% improvement in abdominal pain on at least 50% of days with available electronic patient-reported outcome diary entries as compared to the patient’s worst abdominal pain reported in the screening/run-in phase (‘baseline abdominal pain’).

³The median proportion of days with an at least 30% improvement in abdominal pain compared to the patient’s worst abdominal pain documented in the screening/run-in phase.

Data are presented as absolute numbers and percent of group or median with interquartile range. Risk difference for proportional variables and mean differences for normally distributed variables, with 95% confidence intervals are given. Odds ratio is provided for proportional variables. BSFS: Bristol Stool Form Scale; N/A: Not available; PSQ: Perceived Stress Questionnaire; SF-12: 12-item Short Form survey; IBS-SSS: Irritable Bowel Syndrome-Symptoms Severity Scale; IQR: Interquartile range; RD: Risk difference; MD: Mean differences; CI: Confidence intervals.