Brain Neuronal Networks, Chemosensory and Trigeminal Functions in Allo-HSCT

Study Overview
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Brief Summary
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The goal of this prospective, cohort study is to learn about smell, taste and trigeminal dysfunction in patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). The research team hypothesizes that treatment with allo-HSCT will induce: Distortion of taste and smell and trigeminal functions like cooling, tingling, and burning sensations. Reduced saliva production leading to oral dryness and dental caries. Changes in the connectivity of the taste-, smell- and pain-cortical brain regions.

Detailed Description
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Participants will undergo various tests: Smell function assessment with Sniffin' Sticks. Taste function assessment with Taste Strips. Oral trigeminal function assessment with von Frey filaments . Salivary assessment with the Summated Xerostomia Inventory-Dutch questionnaire. Salivary flow will be measured using salivary flow rate - stimulated whole saliva (SWS). A clinical oral examination will be done to obtain a Clinical Oral Dryness Score. Qualitative smell, taste and trigeminal dysfunction will be assessed using a questionnaire. Radiological and clinical examinations will be performed to evaluate dental and oral mucosal status. Quality of life using questionnaire. Nutritional status using questionnaire. Magnetic resonance imaging of the brain will be taken to capture regions-of-interest for the three different networks of interest; (i) the gustatory network reflecting changes in taste perception, (ii) the olfactory network, related to the changes in smell, and (iii) the pain matrix reflecting pain. There will be a comparisons between the patients and healthy controls.

Official Title
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BrainFlavor: Brain Neuronal Networks and Chemosensory and Trigeminal Functions in Allogeneic Hematopoietic Stem Cell Transplantation - a Prospective Cohort-study

Conditions
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Hematopoietic Stem Cell Transplantation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • patients receiving myeloablative conditioning for a first-time allo-HSCT and diagnosed with either a leukemia or a myelodysplastic syndrome Exclusion Criteria: disorders affecting the oral cavity including poor tooth-status those using drugs affecting the gustatory/olfactory functions those with brain disorders those who have a chronic disorder affecting the immune system, have cancer or who are pregnant.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>Adult recipients of allo-HCST. | |
| Controls<br>Healthy adult subjects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Olfactory (smell) function | Odour pens of the Sniffin' Sticks (Burghart Messtechnik, Wedel, Germany) will be used to test olfactory function (TDI). Scores will range from 0 - 48 where score ≤ 16.5 = anosmia (no sense of smell), score 16.6 - 30.5 = hyposmia (reduced sense of smell) and score >30.5 = normosmia (normal sense of smell) | 1 year | 
| Self-reported olfactory (smell) function | Self-reported smell function will be assessed using a visual analogue scale (VAS) ranging from 0-10 where 0 indicates no smell function and 10 very good smell function. | 1 year | 
| Gustatory (taste) function | Taste function will be evaluated by using taste strips (Taste Strips Burghart Messtechnik, Wedel, Germany) with four basic taste qualities (sweet, sour, salty and bitter) in 4 different concentrations each. Scores will range from 0 - 16 where 0 = ageusia (no sense of taste), 1 - 9 = hypogeusia (reduced sense of smell) and 10 - 16 = normogeusia (normal sense of taste) | 1 year | 
| Self-reported gustatory (taste) function | Self-reported taste function will be assessed using a visual analogue scale (VAS) ranging from 0-10 where 0 indicates no taste function and 10 very good taste function. | 1 year | 
| Oral pain assessment | Oral pain perception will be assessed by von Frey filaments. Scores will range from 0 -10 on a visual analogue scale (VAS) where 0 indicates no pain and 10 severe pain. | 1 year | 
| Self-reported oral pain assessment | Self-reported oral pain will be assessed using a visual analogue scale (VAS) ranging from 0-10 where 0 indicates no oral pain and 10 severe oral pain. | 1 year | 
| Functional brain connectivity | Functional connectivity analysis (fMRI) of three different networks of interest: (i) the olfactory network (ii) the gustatory, and (iii) the pain matrix. There are no specified quantitative units for these measurements. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measured oral dryness | Saliva production will be measured using salivary flow rate - stimulated whole saliva (SWS). Hyposalivation is defined as a salivary secretion rate of ≤0.7 mL/min for SWS. | 1 year | 
| Clinical oral dryness | Clinical oral dryness will be assessed using Clinical Oral Dryness Score (CODS). Scores will range from 0 to 10 points. Score 1-3 is considered mild oral dryness, 4-6 moderate and 7-10 severe oral dryness. | 1 year | 
| Self-reported oral dryness | Self-reported oral dryness will be assessed using the Xerostomia Inventory (XI) questionnaire. Scores will range from 11 to 55 points, with values <14 considered as normal. | 1 year | 
| Oral mucosal status | Oral mucosal status will be evaluated using mucosal-plaque index (MPS). Scores will range from 2 - 8 where 2 - 4 = good/acceptable, 5 - 6 = no acceptable and 7 - 8 = poor status | 1 year | 
| Oral mucositis status | Oral mucosal status will be evaluated using the WHO mucositis grading ranging form 0 - 4 where 0 = no oral mucositis, 1 = erythema and soreness, 2 = ulcers, able to eat solids, 3 = ulcers, requires a liquid diet (due to mucositis), 4 = ulcers, alimentation not possible (due to mucositis) | 1 year | 
| Nutritional status | Nutritional status will be evaluated using the Nutrition Risk Screening 2002 form. Scores range from 0-6. Patients with a score < 3 is considered to be of no nutritional risk. Patients with a score ≥ 3 is considered to be in nutritional risk. | 1 year | 
| Quality of life evaluation | Quality of life will be assessed using the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30). Scores range from 0-100. A high score indicates better quality of life and a low score indicates a worse quality of life. | 1 year | 
| Oral health-related quality of life evaluation | Oral health-related quality of life will be assessed using the Oral Health Impact Profile-14 (OHIP-14) questionnaire. Scores range from 0-56. A high score indicates worse oral health-related quality of life, while a low score indicates better. | 1 year |