Monitor the Impact of The SMA Modified Diet
Research type
Research Study
Full title
Monitor the impact of The Spinal Muscular Atrophy Modified Diet on gastrointestinal and body composition outcomes
IRAS ID
295489
Contact name
Graeme O'Connor
Contact email
Sponsor organisation
Great Ormond Street Hospital
Clinicaltrials.gov Identifier
6843, Research Registry
Duration of Study in the UK
1 years, 6 months, 2 days
Research summary
Research Summary
Spinal muscular atrophy type 1 (SMA1) is a disease that affects the nervous system. SMA1 is the most common neurological system disorder leading to infant death [1]. It is characterized by gradual breakdown of the nervous system leading to progressive muscle weakness eventually causing respiratory failure [2]. This nervous system disease also affects other organs in the body including, pancreas, liver and the gastrointestinal tract [3]. Various studies, including ours, have reported more generalised cellular (metabolic) abnormalities, altering fat and glucose metabolism resulting in abnormal levels in the blood [4]. Due to advances in medication, survival rates have significantly improved in children with SMA 1, with an increasing percentage surviving beyond the typical lifespan of 2 years of age [5]. This achievement has shed light on the metabolic (blood glucose and fats) issues that exist alongside the nervous system problems.
Children with SMA 1 incurr the highest disease burden significantly affecting their quality of life [14]. Thereby, improving their nutritional and metabolic status may reduce the impact of some of the associated symptoms of the disease, including oral and gastrointestinal problems, sleep disorders and sweating.
SMA Modified Diet:
The Amino Acid Diet is a nutritional approach that many SMA families believe has had a positive impact on their child’s quality of life. Using this dietary approach, milk and soy based formulas are eliminated and substituted with a low-fat, elemental free form amino acid formula. Elemental formulas are made from nutrients in their most broken down form, which require very little digestion. An increasing number of SMA families have started the Modified Amino Acid (AA) diet, which has grown in popularity over the last few years following positive feedback from parents, mostly via social media outlets. The AAdiet (http://www.aadietinfo.com) is characterized by high carbohydrates and low fat (~10%). Families also add probiotics to the formula.Sadly, dietitians and medical teams are unable to endorse this diet as there is no evidence available meaning families are often left feeling unsupported and frustrated.
This pilot study was designed with SMA patients and families, and the founder of the SMA Modified Diet. Two consultation workshops were delivered on MS Teams to establish what a Modified AA diet consists of and what was a reasonable and safe compromise.
Summary of Results
With the development of disease modifying treatments children with SMA Type I are living beyond the previous four to five years life expectancy but continue to be affected by the highest disease burden. Our pilot study suggests that children with SMA Type I who are displaying gastrointestinal symptoms, especially when constipation is as a key feature of their clinical phenotype, may benefit from an amino acid formula.
It has been reported that 43% of children with SMA Type I suffer from severe constipation, with abdominal pain and meteorism reported in 15% and 14%, respectively36. This is significantly higher when compared to childhood constipation in the general population, which ranges from 0.7% to 29.6% (median 8.9; inter quartile range 5.3–17.4).37 SMAAF, our simplified version of the traditional SMA amino acid diet had the most significant impact in children who suffered from constipation and required daily medication to regulate their bowel functions.
Fourteen children were recruited from June 2021 to May 2022, with a mean age of 4.1 years (1.2 SD), of which 64% were female. The mean WAZ at baseline was -0.7 (0.9SD). At recruitment, all 14 children required manual mechanical insufflation–exsufflation at least twice a day, with 11 of 14 (78%) requiring non-invasive ventilation - biphasic positive airway pressure for at least 12 hours. All children were receiving Nusinersen, an approved disease modifying treatment for SMA. Demographic characteristics of the cohort can be found in Table 2.
Most children (50%; 7 of 14) were on a standard 1kcal/ ml whole protein enteral formula prior to trialling SMAAF; whereas, 3 out of 14 (21%) were already on an amino acid formula (without probiotics). A full breakdown of feed formulas can be seen in Table 2. Indirect Calorimetry was measured at the start of the study to assess energy requirements and respiratory quotient. The mean resting energy expenditure was 803 kcal (103 SD), which equated to 51.5 kcal/ kg (7 SD). The mean respiratory quotient was 0.80 (0.05 SD) (Table 3). An analysis of variance was used to compare resting energy requirements between indirect calorimetry measurements and predictive energy equations (Schofield equation 35 and Spinal muscular atrophy equation 31) there was no significant difference between values, p value 0.7 and 0.6, respectively (Table 3). A breakdown of key nutritional components of children on SMAAF can be viewed in Table 4.
The most common gastrointestinal complaint reported prior to switching to SMAAF was constipation, present in 12 of 14 (85%) children, of which 10 of the 12 (83%) children required daily stool softeners/laxatives were used to help regulate bowel function. Reflux was reported in 5 of 14 (35%) children (Table 4). Within one week of switching to SMAAF families reported a significant improvement in constipation symptoms.
Eight of the 10 (80%) children who received stool softeners/laxatives saw an improvement in constipation symptoms and either stopped or reduced medication (from daily to prescribed as required). All three children who were previously on standard amino acid formula prior to switch to amino acid formula with added pre and probiotics reported an improvement in stool consistency and frequency.
Stool consistency (as per Bristol stool chart classification) significantly improved from baseline compared to end of study (week 8) in children who switched to SMAAF; 2.2 (0.4SD) vs 3.6 (0.4SD) p< 0.001; CI 2.72-3.72, respectively. Similarly, stool frequency (bowel movements per week) increased from baseline compared to end of study (week 8) from 3.6 (1.08SD) vs 4.9 (0.45SD) per week; p< 0.09, CI -0.65-2, respectively.
Improvements in reflux was seen in 4 of 5 (80%) children, and a reduction in oral secretion was reported in 6 of 14 (43%) children (Table 5). Although some parents reported a reduction in reflux and oral secretion in respect to mouth wiping or mucus volume suctioned whilst receiving SMAAF, this was not captured in parent diaries and warrants further discussion how best to capture this outcome Appropriate weight gain was observed while children were following SMAAF for the eight-week trial (baseline WAZ score: -0.7 [0.9 SD] vs 8-weeks -0.5 [0.7 SD], p=.03).
Advances in SMA Type I therapy poses new challenges, particularly in relation to the management of gastrointestinal symptoms and liver disorders. Children with SMA Type I who are displaying gastrointestinal symptoms such as constipation and reflux may benefit from an amino acid formula that is fortified with probiotics. More research into fatty acid metabolism and manipulation of type of fats in children with SMA Type I is warranted.REC name
West of Scotland REC 5
REC reference
21/WS/0074
Date of REC Opinion
9 Jul 2021
REC opinion
Further Information Favourable Opinion