Randomized controlled trial protocol to analyze the effects of rice with different contents of resistant starch on chronic constipation

Abstract

The trend of the aging population worldwide is becoming increasingly severe. As people age, constipation becomes increasingly common in older adults, causing varying degrees of physical and psychological harm to them. Dietary intervention is a common nonpharmacological therapy. Resistant starch is a type of dietary fiber that can regulate the gut microbiota and alleviate chronic constipation. However, few studies have explored the effects of different types of rice on chronic constipation in older adults. This protocol aims to evaluate the effects of rice with different contents of resistant starch on chronic constipation in old adults. This trial is a double-blind, two-arm randomized controlled trial. Older adults with chronic constipation residing in long-term care facilities will be recruited. Participants will be randomly assigned to receive A rice (resistant starch: 11-20%) or receive B rice (resistant starch: 0.1-0.5%). Both groups will adopt the serving of individual dishes, and the nutrition experts calculated the consumption of rice in the two groups according to the different conditions of each older person to ensure that the number of calories in the meal remained unchanged and that the other dietary components remained unchanged. The intervention will last for a total of 24 weeks. Participants will undergo follow-up via questionnaires at 6, 12, and 24 weeks during the intervention. The primary outcome will be constipation symptoms assessed by the Wexner questionnaire. The secondary outcomes will be quality of life, depression, anxiety and sleep quality. This is the first randomized controlled trial on the effects of rice with different contents of resistant starch on chronic constipation in older adults. It is expected that this study, if proven effective in relieving constipation symptoms in older adults, will provide evidence-based constipation care for medical staff.

Trial registration number: retrospectively registered on Chinese Clinical Trial Registry.

Introduction

The world’s population is aging at an unprecedented rate, and the number of people aged 60 years and above is expected to increase to more than 2 billion by 2050¹. As age increases, the mechanical properties, macroscopic structure, and pelvic floor control ability weaken, which affects the structure and function of the intestine, leading to a decrease in colon propulsion and an increase in fecal transport time^2,3. Therefore, older adults have decreased gastrointestinal motility, weakened defecation reflex function, and decreased rectal sensitivity and are more susceptible to constipation compared to young people. The prevalence of constipation globally for adults over the age of 65 years is estimated to be 30% ⁴. Constipation often causes dual physiological and psychological harm to older adults^5,6. Constipation can cause abdominal pain and loss of appetite and can easily lead to serious anorectal complications, such as hemorrhoids, bleeding, and fecal impaction⁷. In addition, older adults with constipation are prone to coexisting with depression and anxiety. A previous study has shown that 49% of constipation patients exhibit depressive symptoms⁸. However, psychological factors such as anxiety and depression can in turn affect the sensation, movement, and secretion functions of the gastrointestinal tract in older adults⁹, leading to the occurrence and aggravation of constipation¹⁰, further exacerbating psychological distress and forming a vicious cycle. Therefore, constipation seriously affects the quality of life of older adults, and there is an urgent need to explore effective methods to treat constipation.

The main clinical treatment for constipation in older adults is pharmacological therapy, but long-term medication can easily lead to drug dependence, with prominent side effects¹¹. Dietary intervention is a common non-pharmacological therapy, and increasing crude fiber content in the diet can effectively alleviate constipation symptoms^12,13. Resistant starch, a healthy carbohydrate component in the diet, has recently received much attention¹⁴. Resistant starch is not digested in the small intestine and can thus affect the gut microbiota of the host because of its fermentability¹⁴. In addition, the resistant starch in rice can regulate the intestinal microbiota and improve chronic constipation¹⁵. A randomized controlled trial demonstrated that high doses of resistant starch can effectively alleviate constipation and increase beneficial health-associated bacteria¹⁶. Using resistant starch to intervene in constipation symptoms in older adults may be a very convenient and highly accepted self-management method. Therefore, the aim of this study is to evaluate the efficacy of rice with different contents of resistant starch in treating chronic constipation in older adults. The hypothesis is that resistant starch at high doses (resistant starch: 11-20%) may be more effective than resistant starch at low doses (resistant starch: 0.1-0.5%) with respect to alleviating chronic constipation.

Methods

This study is a double-blind, two-arm randomized controlled trial with randomization at the participant level. This trial was approved by the Ethics Committee of West China Hospital of Sichuan University (number: 2023 − 1180) and we confirm that all experiments will be performed in accordance with relevant guidelines and regulations. This protocol followed the statement of the Protocol of a Clinical Trial (SPIRIT)¹⁷. The constipation score will be the primary endpoint for examining whether high doses of resistant starch alleviate chronic constipation in older adults. All outcomes will be collected for the two groups at baseline (T0), at 6 week (T1), at 12 weeks(T2) and at 24 weeks (T3) during the intervention. The overview of the study design is shown in Fig. 1.

Fig. 1.

Study design.

Study setting and recruitment

This trial will be conducted at a nursing home in Chengdu, China. The recruitment program for participants is planned to start in September 2024 and is expected to conclude by October 2025. Older adults aged 60 years and older with chronic constipation will be recruited. Through flyers, researchers will approach potentially eligible participants in the nursing home, and describe the study purpose and general content to them.

The inclusion criteria for participants are as follows: (1) aged 60 years old and above; (2) meet the Rome III diagnostic criteria; (3) have a duration of constipation greater than 6 months; and (4) voluntarily participate in this study and sign an informed consent form. The exclusion criteria are (1) irritable bowel syndrome; (2) organic gastrointestinal diseases; (3) drug-induced constipation; (4) other organic diseases or mental illnesses; and (5) use of medications to treat constipation or take medications that affect intestinal peristalsis for a long time. Patients who do not follow the intervention plan or who do not consume all food given three times a week will be removed from the study. The researchers will once again describe the details of the study to interested patients who are eligible, obtain a written consent form, and collect baseline data.

To calculate the sample size, we plan to conduct a pilot study, and it is suggested that a general flat rule of a pilot study is to recruit at least 30 participants^18–20. The sample size will be calculated using PASS 15.0 software based on the scores of constipation symptoms after the pilot study.

Randomization

The random number table will be generated based on random variable. The uniform function of SPSS 26.0 software will be used. After assessment at baseline, eligible participants will be randomly assigned to one of two groups at a 1:1 ratio after the initial evaluation. Participants will be randomly allocated via an online service provided by the Innovation Center of Nursing Research at the West China Hospital.

Blinding

We cannot allow researchers to be blinded to the assigned interventions because they need to distribute food to participants. The rice of different amount of resistant starch is similar that it can not be distinguished by participants. So, participants will be blinded. In addition, the data collector and statisticians will be blinded to participants’ allocation. Full concealment of allocation will be ensured. The randomization of participants will be conducted by a non-researcher outside the study by using sealed envelopes. The allocated interventions have been placed in sealed envelopes and the researchers who will implement interventions will receive the sealed envelopes.

Interventions

All participants will be randomly assigned to the experimental group, which will receive A rice (resistant starch: 11-20%), or the control group, which will receive B rice (resistant starch: 0.1-0.5%), at a 1:1 ratio after the initial evaluation. After moving into the nursing home, all participants will receive usual care, including providing patients with health education and nursing care and informing patients and their families of relevant knowledge about chronic constipation. Participants and their families should know that constipation can lead to anal fissures and hemorrhoids. In severe cases, it can also worsen the original disease.

The main staple food of the participants in the experimental group will be A rice, with a resistant starch content of 11-20% (production license number: SC10151018400603). Participants in the control group will eat regular rice, with a resistant starch content of 0.1-0.5% (production license number: SC10123018404873). The detailed information of both A rice and B rice can be found at http://www.qszt.net/. Macronutrients of 2 different rice are shown in Table 1. Both groups of participants will be determined by nutrition experts based on the weight and physical condition of the older adults, ensuring that each older person’s dietary calories and nutrition remain unchanged. Food given, water intake, medications, and exercise will be recorded by participants’ caregiver. As observed and controlled by the staff of the nursing home, participants’ exercise and water intake habits will not show significant changes during the intervention process. The data of food, water, medications, and exercise will be summarized and provided to the researchers. Each participant will eat daily at 8:00, 12:00, and 18:00. Except for different types of rice, the rest of the food in both groups will be the same. In addition, each meal will be supervised by nursing staff to ensure that participants will eat on time and in the appropriate amount, and to observe and prevent food exchange between participants.

Table 1.

Comparison of macronutrients of 2 different rice.

Items	Per 100 g		Nutrient reference values
	A rice	B rice	A rice	B rice
Energy	1484 KJ	1480 KJ	18%	18%
Protein	7.12 g	5.8 g	12%	10%
Fat	0.3 g	0 g	1%	0%
Carbohydrate	79.5 g	80.2 g	27%	27%
Sodium	3.31 mg	0 mg	0%	0%

Outcome assessment

A research assistant will perform the data collection. Demographic data will be collected at baseline (T0). All outcomes will be collected for the two groups at baseline (T0), at 6 week (T1), at 12 weeks(T2) and at 24 weeks (T3) during the intervention. The primary outcome will be constipation symptoms. The secondary outcomes will be quality of life, depression, anxiety and sleep quality.

Demographic data (T0)

To characterize the participants, sex, age, educational level, marital status, monthly income per capita of family, duration of constipation, weekly bowel movements, duration of each bowel movement, chronic disease status, main caregivers, rice intake, water intake, medications, and exercise habit will be collected.

Constipation symptoms

The Wexner questionnaire, developed in 1996 by Dr. Wexner, will be used to evaluate constipation symptoms²¹. This questionnaire has eight items that are graded on a five-point Likert scale except for one, which is scored from 0 to 2. The total score ranges from 0 to 30, and a higher total score indicates more severe constipation symptoms.

Quality of life

The Patient Assessment of Constipation Quality of Life questionnaire was developed by Marquis et al. to evaluate the effects of constipation on patients’ quality of life, which will be used to assess quality of life in older adults with constipation²². This questionnaire contains 4 dimensions and 28 items, including physical discomfort, psychosocial discomfort, worries and concerns, and treatment satisfaction. Each item is scored from 0 (not at all) to 4 (all of the time). The total score ranges from 0 to 112. The higher the score is, the greater the negative impact of constipation on the patient’s quality of life.

Depression

The Zung Self-Rating Depression Scale will be used to evaluate subjective feelings within 2 weeks²³. This scale consists of 20 items. Each item is scored from 1 (not at all) to 4 (all of the time). The total score is multiplied by 1.25, which ranges from 25 to 100. A final total score of < 50 denotes a “normal” mood. The higher the score is, the more severe the depression.

Anxiety

The anxiety of older adults with constipation will be measured by using the Zung Self-Rating Anxiety Scale, which can measure mood over the previous week²⁴. This scale has 20 items, and each item is scored from 1 (not at all) to 4 (all of the time). The raw score ranges from 20 to 80, and the standard score should be calculated by multiplying the raw score by 1.25. Therefore, the total standard score ranges from 25 to 100. Anxiety is defined as a total standard score ≥ 50. The higher the score is, the more severe the anxiety.

Sleep quality

The Self-Rating Scale of Sleep was developed by Li²⁵ and will be used to evaluate the sleep quality of older adults with constipation. This scale has ten items, and each item is scored from 1 to 5. The total score ranges from 10 to 50. The higher the score is, the worse the sleep quality.

Statistical analysis plan

We will use IBM SPSS Statistics 26 to analyze the data. Confidence intervals will be stated at the 95% confidence level. The normality of the distribution of measurement data will be tested by using a P‒P diagram and a Q‒Q diagram. Normally distributed measurement data will be presented as the mean and standard deviation. Otherwise, the median and quartile will be used for statistical description. If measurement data follow a normal distribution and homogeneity of variance, they will be compared by the independent sample t-test for intergroup comparisons, and a paired-sample t-test will be used for intragroup comparisons. Otherwise, the Mann‒Whitney U test will be used for intergroup comparisons, and the Wilcoxon signed rank sum test will be used for intragroup comparisons. After testing the homogeneity of variance and spherical hypothesis, we will use repeated measurement analysis of variance to test repeated measurement data and use Greenhouse Geisser to correct data that do not meet the spherical symmetry condition. The number and percentage will be used to describe counting data. Fisher’s exact test will be used to test the counting data. If the baseline indicators are not comparable, an adjustment to the efficacy contrast of variables, such as sex, age, educational level, constipation duration, weekly bowel movements, or duration of each bowel movement, is needed. The covariance approach and logistic regression analysis will be used for continuous variables and counting data, respectively. Statistical significance is defined as P < 0.05. All tests are 2-sided.

Discussion

This study presents a protocol of a double-blinded, two-arm randomized controlled trial targeting older adults with chronic constipation. With this study, we will evaluate the effects of rice with different contents of resistant starch on chronic constipation in old adults, and we expect this method to alleviate chronic constipation in older adults. The novelty of this study lies in its emphasis on daily diet as a highly accepted method for alleviating constipation in older adults. In addition, this study can help to identify rice varieties suitable for older adults with chronic constipation.

Resistant starch is defined as a beneficial dietary fiber because it cannot be digested in the gastrointestinal tract²⁶. Whole rice is the main staple food for large populations worldwide. It contains many macronutrients, including starch. However, in cooked regular whole rice, there is usually only a small amount of resistant starch, which has been proven to be very beneficial for improving the gut microbiota and producing health-promoting metabolites^27–29. In addition, it has been proven that stool consistency is strongly associated with gut microbiota richness and composition³⁰. Thus, resistant starch may alter stool consistency and alleviate constipation by regulating the gut microbiota. Moreover, the results of an animal experiment suggested that resistant starch is the best fiber source for promoting gut motility, as it is related to the levels of 5-hydroxytryptamine under specific bacteria and butyrate stimulation, thereby relieving constipation³¹. Based on but not limited to the above theoretical and practical foundations, this study will focus on resistant starch and the use of rice with different contents of resistant starch to intervene in chronic constipation in older adults. We assume that compared to regular rice consumption, consuming rice with high-dose resistant starch as a staple food can effectively alleviate chronic constipation in older adults.

Conclusion

This will be one of the few randomized controlled trials to evaluate the impact of rice with different contents of resistant starch on chronic constipation in old adults. The results may provide some important references for future clinical treatment and research on chronic constipation. However, this is a single-center study and our findings may not generalize to older adults seen in other nursing home. So, a multi-center randomized controlled trial should be considered in the future.

Trial status

Recruiting patients will start in September 2024 and is expected to conclude by October of 2025.

Author contributions

Yiping Zhao and Xiuying Hu conceived the study. Yiping Zhao, Fanyu Zhao, Qian Liu, Li Liu and Xiuying Hu contributed to the design of this study. Yiping Zhao drafted the manuscript. Yiping Zhao and Fanyu Zhao modified this manuscript. Fanyu Zhao, Qian Liu and Fang Wang critically reviewed the manuscript for important intellectual content. All authors read and approved the final manuscript.

Funding

This work was funded by Sichuan Provincial Administration of Traditional Chinese Medicine (grant number 2023MS405).

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Ethical approval for this trial was obtained from the Ethics Committee of West China Hospital of Sichuan University (number: 2023 − 1180). Researchers will inform participants about the potential harms and benefits of this study. Written informed consent will be obtained from all participants.