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Efficacy and Clinical Evidence

Clinical Studies

STUDY #1:

Robayo-Torres CC, et al. 13C breath tests for sucrose digestion in congenital sucrase isomaltase-deficient and sacrosidase-supplemented patients. J Pediatr Gastroenterol Nutr. 2009;48:412-418.

In this study, Robayo-Torres and colleagues examined both the ability of a 13C-labeled breath test to detect Genetic
Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency without the need for a duodenal biopsy and the effect of sacrosidase supplementation on breath test results. A total of 10 Genetic Sucrase-Isomaltase Deficiency patients (diagnosed by low biopsy sucrase activity) and 10 control patients who had undergone endoscopy and biopsy because of dyspepsia or chronic diarrhea, but with normal mucosal enzyme activity, were tested. Patients were separately administered uniformly labeled oral 13C-glucose and 13C-sucrose loads. After each administration, 13C-CO2 breath enrichment was assayed using an infrared spectrophotometer. Tests were repeated after adding Sucraid®. Results were measured by calculating the mean percentage coefficient of glucose oxidation (%CGO).

Results

Csid gsid sucraid study graph

Figure 1

Effects of CSID on oral %CGO.
[Robayo-Torres CC, Opekun AR, Quezada-Calvillo R, et al. J Pediatr Gastroenterol Nutr. 2009]

In the control group, there was an average of 146% ± 45.5% mean percentage coefficient of glucose oxidation (%CGO); in contrast, the %CGO in the CSID group was 25% ± 21% (P<.001), demonstrating that 13C-breath testing clearly distinguished among patients with and without Genetic Sucrase-Isomaltase Deficiency (Figure 1).

The test had 100% sensitivity and 100% specificity (confidence interval = 74-100%) for detection of low duodenal sucrase activity. All patients with Genetic Sucrase-Isomaltase Deficiency showed a correction of sucrase deficiency with oral Sucraid® supplementation (Figure 2; P=.001).

Conclusions
gsid sucraid study table

Figure 2

Effect of oral sacrosidase supplementation of CSID patients on sucrose breath test %CGO. [Robayo-Torres CC, Opekun AR, Quezada-Calvillo R, et al. J Pediatr Gastroenterol Nutr. 2009]

The 13C-sucrose breath test was accurate and specific as a noninvasive confirmatory test of CSID. All patients with Genetic Sucrase-Isomaltase Deficiency showed correction of sucrase deficiency with oral Sucraid® supplementation.


STUDY #2:

Treem WR, et al. Sacrosidase therapy for congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr. 1999;28:137-142.

In a study published in 1999 by Treem and colleagues, the efficacy and safety of sacrosidase oral solution was examined in children with confirmed Genetic Sucrase-Isomaltase Deficiency consuming a normal sucrose- and carbohydrate-containing diet.

Patients

Patients with Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency were recruited from the practices of members of the North American Society for Pediatric Gastroenterology. Criteria for inclusion were:

  • History of chronic watery diarrhea with an acid pH <6.0
  • Small intestinal biopsy specimens with measurement of tissue disaccharidase levels
  • Sucrase activity <10% of control specimens
  • Normal or decreased maltase activity
  • Normal lactase levels and a normal result in a lactose breath hydrogen test
  • Normal villous architecture of the small intestine

There were a total of 28 patients with Genetic Sucrase-Isomaltase Deficiency enrolled in this randomized, multicenter, double-blind, controlled trial. All patients were infants or children (12 boys) between the ages of 5 months and 11.5 years (mean age, 4 years; median, 2.5 years). At baseline, the mean body weight of subjects was 16.5 kg.

Study Design and Treatments

The trial consisted of two phases (Figure 3). The breath hydrogen phase consisted of three single-dose treatments (placebo, sacrosidase and sacrosidase with milk). Patients were subsequently randomized to one of four doses of sacrosidase for a 10-day treatment period, and crossed over to other dosages in random order until a 40-day treatment period was completed. Dosing of sacrosidase was weight-dependent: 1 mL/meal if weight was ≤15 kg; 2 mL/meal if >15 kg.

Csid gsid sucraid breath tests

Figure 3

Study design. [Treem WR, McAdams L, Stanford L, Kastoff G, Justinich C, Hyams J. J Pediatr Gastroenterol Nutr. 1999]

Assessments and End Points

Stool frequency and consistency measures, symptoms and dietary data were recorded daily and compared with a baseline period in which patients had consumed a sucrose-free diet without sacrosidase. Dietary assessment of sucrose and carbohydrate consumption was summarized for each treatment period during the dose-response phase to verify whether patients were compliant with a “normal” diet (2 g/kg/d sucrose and 5 g/kg/d carbohydrate).

The primary efficacy variables included total stools and total symptoms scores collected during the dose-response phase. All other measurements were secondary. During the dose-response phase, the number of stools and severity of symptoms (gas, bloating, nausea, vomiting and abdominal cramps) were recorded daily by each patient and assigned values ranging from zero (none) to three (severe). A post hoc responder assessment (asymptomatic yes/no) was also determined.

Results

Of the 28 patients in this trial who received ≥1 dose of sacrosidase, 26 (93%) completed the trial.

In the placebo phase, of the 28 patients in the trial who consumed a sucrose-free diet, the percentage reporting severe or moderate gastrointestinal symptoms was as follows: 75% diarrhea, 67% gas, 60% stomach pain and 20% nausea.

In the dose response phases, significant differences were observed between the two higher concentrations (undiluted and 1:10 dilution) and the two lower concentrations (1:100 and 1:1,000 dilution) for both of the primary outcome variables—total stools and total symptoms score (Figure 4).

Number of stools in 10 days

Sacrosidase treatment Stools/d (mean ± SEM) Watery Soft Formed Hard Total symptoms score ≤7 (%)
Full strength 1.82 ± 1.6* 3.8 ± 1.7 6.1 ± 1.4 7.9 ± 1.2 0.4 ± 0.2 70*
1:10 2.20 ± 2.5 7.0 ± 2.8 7.0 ± 1.2 7.7 ± 1.7 0.1 ± 0.1 63
1:100 2.58 ± 2.9 12.0 ± 3.3 8.3 ± 1.3 5.1 ± 1.1 0.1 ± 0.1 54
1:1000 2.44 ± 2.5 9.7 ± 2.3 9.0 ± 1.5 5.4 ± 1.1 0.3 ± 0.3 54
Baseline 2.31 ± 2.2 82

Figure 4

Effect of sacrosidase on stools and stool consistency while consuming a sucrose-containing diet. *Significant differences were shown between the two higher and two lower concentrations for total stools (P≤.001) and total symptoms score (P=.003). [Treem WR, McAdams L, Stanford L, Kastoff G, Justinich C, Hyams J. J Pediatr Gastroenterol Nutr. 1999]

Overall, 81% of patients were asymptomatic while receiving full-strength sacrosidase. Analysis of the overall symptomatic response, as a function of age, indicated that in CSID patients up to 3 years of age, 86% became asymptomatic. In patients aged ≥3 years, 77% became asymptomatic, suggesting that therapeutic response does not differ significantly according to age (Figure 5).

Only four patients in the trial experienced adverse events, including wheezing, vomiting, pallor and dehydration. Three completed the trial and continued in an open-label trial with sacrosidase. The remaining patient, who was hospitalized for wheezing and withdrew from the trial, had pre-existing asthma. Most of the adverse events were attributed to concurrent illnesses common in childhood and were probably unrelated to sacrosidase. Click here for additional important safety information about Sucraid®.

Conclusions
Csid-sucraid-asymptomatic-patients-table

Figure 5

Patients becoming asymptomatic after treatment with Sucraid®,
by age (P=.01 vs baseline; N=28). [Data on file, QOL Medical. 1998]

The results of this trial indicate that sacrosidase is an effective treatment for Genetic Sucrase-Isomaltase Deficiency. By taking sacrosidase with each meal, patients were able to eat a more normal carbohydrate- and sucrose-containing diet without developing major gastrointestinal symptoms. This study indicates that use of sacrosidase may reduce the high incidence of GI complaints in this patient population.


STUDY #3:

Treem WR, et al. Evaluation of the liquid yeast-derived sucrase enzyme replacement in patients with sucrase-isomaltase deficiency. Gastroenterology. 1993;105:1061-1068.

In this study, published by Treem and colleagues in 1993, the ability of sacrosidase to reduce the breath hydrogen response to an oral sucrose test was examined. Additionally, the ability of sacrosidase to reduce symptoms of sucrose malabsorption was assessed.

Study Design

A variety of methods was used to examine the enzymatic quality and stability of sacrosidase. The clinical activity of sacrosidase was evaluated in patients with a positive diagnosis of Genetic Sucrase-Isomaltase Deficiency who underwent double-blind, placebo-controlled breath hydrogen tests, followed by an eight-week dose-response study conducted while consuming a diet containing a moderate amount of sucrose. During this period, patients were treated with four different concentrations of sacrosidase for 14 days each.

Results

Sacrosidase was found to be stable at 4˚C and retained full activity between pH 1.0 and 6.2. Pepsin digestion of the enzyme in vitro was completely eliminated by bovine serum albumin.

gsid sucraid chart

Figure 6

Symptomatic response of patients (N=12) to increasing dilutions of sacrosidase when consuming a sucrose-containing diet. Dilutions ranged from 1:100 to 1:100,000.*, >3 stools/d for ≥2 days of the 14-day field trial; [square], diarrhea on any day of the 14-day period; [circle], abdominal pain on any day of the 14-day period; [triangle], excessive gas on any day of the 14-day period. Adapted from Treem et al, 1993. [Treem WR, Ahsan N, Sullivan B, et al. Gastroenterology. 1993]

A total of 14 patients with Genetic Sucrase-Isomaltase Deficiency (five male; mean age 7.6 years) were enrolled in the study. All patients had normal lactose breath H2 test results and abnormal sucrose breath H2 tests. Overall, there was a significant reduction in cumulative breath H2 (P<.001) and peak breath H2 (P<.002) when sucrose was ingested with sacrosidase compared with placebo. Twelve patients completed an eight-week field trial of four different concentrations of sacrosidase, ranging from a 1:100 dilution to a 1:100,000 dilution. Of note, there was a strong dose-response relationship, with patients who received the lowest dilution experiencing the fewest symptoms. Most patients tolerated a sucrose-containing diet with minimal symptoms while ingesting 1 ml. of the 1:100-diluted YS with each meal. With increasingly dilute YS, symptoms of diarrhea, abdominal pain and excessive gas were increasingly prevalent (Figure 6). Click here for important safety information for Sucraid®.

Conclusions

In this preliminary study, sacrosidase was shown to be effective in reducing symptoms of CSID. The results indicated that early intervention in patients with CSID might prevent chronic, watery diarrhea and poor weight gain during infancy. There was a clear dose-response relationship in the higher concentrations of sacrosidase, which provided greater efficacy. Sacrosidase was stable at temperatures achievable in domestic refrigerators.


STUDY #4:

Open-label, long-term study of sucrase enzyme therapy for congenital sucrase-isomaltase deficiency. QOL Medical, LLC. OMC-SUC-3. 1997. Data on file.

This uncontrolled open-label, long-term trial evaluated the safety, patient acceptability, and effectiveness of Sucraid® in treating patients with Genetic Sucrase-Isomaltase Deficiency/Congenital Sucrase-Isomaltase Deficiency consuming a sucrose-containing diet. Upon completion of the previous controlled trials involving Sucraid®, 34 Genetic Sucrase-Isomaltase Deficiency patients from 6 months to 28 years of age (median age about 3 years) were allowed to continue treatment with Sucraid® for 2 to 54 months (a total of over 900 months of Sucraid® therapy). Patient dosing varied from currently approved patient dosing.

Results

The 34 patients treated in the trial represent a total of over 900 patient-months of Sucraid® therapy. A total of 31 adverse events were recorded in fourteen patients (41%). Some adverse events were considered as possibly related to treatment, while others were deemed unrelated.

No patients discontinued due to adverse events. Three patients experienced serious adverse events, and all three continued treatment with Sucraid®.

Conclusions

The results of this long-term trial indicate that Sucraid® was well-tolerated and an effective treatment for the gastrointestinal symptoms of Genetic Sucrase-Isomaltase Deficiency as used in this trial. Sucraid® allowed Genetic Sucrase-Isomaltase Deficiency patients enrolled in this study to consume a sucrose-containing diet over the long term by attenuating the characteristic gastrointestinal symptoms of Genetic Sucrase-Isomaltase Deficiency.

QOL Medical, LLC