Clinical trial NCT04398836: Preoperative Nutrition for Crohn's Disease Patients
Official title: Preoperative Nutrition for Crohn's Disease Patients
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Malnutrition
Crohn Disease
Lead sponsor: Tel-Aviv Sourasky Medical Center
Sponsor class: OTHER_GOV
First posted: 2020-05-21
Enrollment: 144
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigator hypothesizes that compliance to Exclusive enteral nutrition (EEN) will be high among patients on an operation for their bowel disease, compared to the compliance rate seen in the general Crohn's Disease (CD) population.

Also,the investigator hypothesizes that clinical outcomes would improve, and post-operative complication rate will be reduces in malnourished CD patients receiving pre-operative 4 weeks EEN during the 4 weeks post-surgery, compared to CD patients receiving high energy and protein diet without EEN.

Detailed description: Study design:

A randomized, none-blinded study. Study population: 144 CD patients designated for surgery, 96 malnourished patients and 44 well-nourished patients. Participants will be recruited from the Department of Gastroenterology, from Surgery Department and from the Nutrition Unit in the Tel Aviv Medical Center (TLVMC).

Study procedure CD patients who are awaiting surgery will be screened and randomly assigned to the study. After the decision to perform surgery and patient's acceptance to participate in the study but not more than 3 months before scheduled surgery, patient will undergo nutritional assessment. Patients suffering from malnutrition will be randomly assigned to the EEN group or to the group receiving enriched high energy and protein diet. Well-nourished patients will continue with standard nutritional therapy. Malnutrition will be defined according to Subjective Global Assessment (SGA)

Screening procedure:

Patients assigned to the interventional arm would be asked to adhere to EEN for two days prior to inclusion in order to assess tolerability and adherence to the assigned diet. Those who are not able to adhere to a two day EEN diet , will be withdrawn from the interventional arm, and will be treated with a high energy, high protein diet as the control group in accordance to the study protocol.

Study group:

Patients will drink an enteral polymeric formula suited to their energy expenditure calculated by 25-30 kcal/kg and at least 1 gr/kg of protein, a minimum of 1500 ml (1500 kcal, 54 gr of protein). The amount of formula to achieve nutritional requirements are based on body weight, but the average intake is of 6-8 cups of formula (36-48 scoops of formula mixed with 1260-1680 ml of water to achieve a concentration of 1 kcal per ml). During period patients guided to avoid eating and drinking anything but the enteral formula. The formula will be supplied to the patients by the investigators.

The formula used for this study will be VITAL - suitable for people with disease-related malnutrition and malabsorption. Vital 1.5kcal is peptide-based, nutritionally complete formulation for the dietary management of active phase of CD. VITAL includes all the nutritional macro and micronutrients and can serve as a sole source of nutrition. In cases of severe nutritional deterioration throughout the study, supplemental parenteral nutrition will be considered.

Control group:

Nutritional support by high energy/high protein diet, calculated by 25-30 kcal/kg and at least 1 gr/kg of protein. In cases of significant nutritional deterioration throughout the study, oral nutritional supplements or supplemental parenteral nutrition will be considered.

Well-nourished patient group: accepted standard nutritional therapy.

Compliance and dietary evaluation:

Patients will fill-up a 3 day food diary during every study visit to assesses recent dietary composition. Adherence to therapy will also monitored using the Medication Adherence Rating Scale (MARS) questionnaire.

Nutrients intake will be computed with the Israeli nutritional software "Zameret". Patients in the EEN group will be required to return the empty enteral formula containers.

Compliance to the diet instructed for the patient will be concidured as intake of 80% of calories per patient.

Compliance to the diet instructed for the patient will be concidured as intake of 80% of calories per patient.

Tolerability to EEN:

Tolerance will be defined as ingestion of the entire amount of formula requested by the patient without the development of any allergic/intolerant symptoms. Tolerance will be monitored during every study visit.

Disease activity:

Disease activity will be evaluated by serum C- Reactive Protein (CRP) concentration, fecal calprotectin concentration and Harvey-Bradshaw index (HBI).

Metabolic evaluation

Anthropometric measurements:

* Weight and height will be measured on a digital medical scale and body mass index (BMI) will be calculated.
* Handgrip strength will be measured by a handgrip dynamometer (JAMAR® - hydraulic hand dynamometer )
* Nutritional assessment by SGA questioners.
* Body composition by body electrical impedance.
* Resting Energy Expenditure (REE) will be measured by indirect calorimetry (Fitmate- Cosmed/ Italy)

Biochemical tests:

All blood samples will be drawn at the morning following 12 hours fast: albumin, blood count, serum CRP concentration and fecal calprotectin concentration.

Post operative clinical course:

Patient post-operative course will be documented from patients medical file. Parameters will include: hospitalization length, blood transfusions and other interventions, post operative medical treatment.

Fecal samples:

Stool will be analyzed for fecal calprotectin and for characterizing the microbial composition

Assessment of surgical complications

The following complications will be monitored 30d after surgery:

* Hospital readmissions
* Revision of surgery
* Stoma complications
* Severe bleeding
* Thrombotic event
* Ileus
* Liver complications
* Renal complications
* Infectious complications: Surgical site infection, Urinary tract infection, Pulmonary; anastomotic leaks, intraabdominal abscess and formation of new fistula.

Safety EEN is an accepted and recommended therapy for CD patients and considered a first-line therapy for inducing remission in children.

Eligibility criteria: Inclusion Criteria:

• CD patients awaiting surgery

Exclusion Criteria:

* Pregnancy and lactation
* Subjects on TPN
* Subjects with chronic conditions such as cancer, organ transplant subjects, advanced kidney or liver disease, systemic inflammatory conditions other than IBD
* Inability to sign informed consent and complete study protocol
* Surgical procedure to reverse ileostomy/colostomy or abscess drainage

Primary outcomes:
measure: Changes in Compliance to diet
timeFrame: during every study visit week 0, week 1, week 2, week 3, week 4, 30 days post - surgery
measure: Changes in adherence to therapy
timeFrame: during every study visit week 1, week 2, week 3, week 4, 30 days post - surgery
measure: Changes in tolerability to the diet
timeFrame: Tolerance will be monitored during every study visit: week 0, week 1, week 2, week 3, week 4
Secondary outcomes:
measure: The rate of post-operative complications in malnourished CD patients receiving pre-operative 4 weeks EEN, is changed during the 4 weeks post-surgery, compared to CD patients receiving high energy and protein diet without EEN one month after surgery.
timeFrame: One month after surgery
Other outcomes:
Locations:
city: Tel Aviv
country: Israel
facility: Dep. of Gastroenterology, Tel Aviv Sourasky Medical Center
Study officials:
affiliation: Tel Aviv Medical Center
name: Nitsan Maharshak, MD
role: PRINCIPAL_INVESTIGATOR
References: