Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients With Medical Xerostomia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-90
SponsorUniversity of Wisconsin, Madison
About this trial
The goal of this clinical trial is to evaluate the safety and tolerability of injecting certain cells produced in bone marrow called mesenchymal stromal cells (MSCs) into salivary glands. The main question it aims to answer is whether injection of MSCs into salivary glands results in any improvement in dry mouth.
Participants will:
* have bone marrow collected using a needle * undergo a salivary gland ultrasound * complete questionnaires * receive an injection of the bone marrow cells into a salivary gland
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Xerostomia, defined as an unstimulated salivary flow <1.2 mL in 5 minutes documented at any time following xerostomia diagnosis and prior to enrollment
Xerostomia not resulting from radiotherapy (medical xerostomia)
≥ 18 years of age, ≤ 90 years of age
Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia
Disqualifiers
Patients with one submandibular gland
Sialolithiasis
Poorly-controlled diabetes mellitus (HbA1c ≥ 7%)
Patients who initiated any diuretic therapy before developing dry mouth symptoms and are still on diuretic therapy and the referring provider believes the dryness symptoms are driven by diuretic use
Trial design
Design model
Sequential
Treatments tested in this trial
Mesenchymal Stromal Cells (MSC) Dose Level 0
Biological/Vaccine10 (8-12) x 10\^6 MSCs
Mesenchymal Stromal Cells (MSC) Dose Level 1
Biological/Vaccine20 (16-24) x 10\^6
Treatment groups
36 Participants
are divided into 3 treatment groupsGroup A: MSCs Dose Level 0 into one submandibular glandActive comparator 1 intervention
Group B: MSCs into both submandibular glands - Dose Escalation CohortActive comparator 2 interventions
Group C: MSCs into both submandibular glands - Expansion CohortActive comparator 2 interventions
Trial outcomes
Primary outcomes
1
Proportion of participants experiencing DLT of submandibular pain
Recommended phase II dose (RP2D) will be determined by the proportion of subjects experiencing the dose-limiting toxicity (DLT) of submandibular pain \> 5 on a standard 10-point pain scale of 0-10 at 1-month after MSC injection
Time frame
1 month post-injection2
Proportion of participants experiencing DLT as serious adverse events (AEs)
RP2D will be determined by the proportion of subjects experiencing the dose-limiting toxicity (DLT) of any serious AE within one-month post-injection
Time frame
1 month post-injection3
Proportion of participants experiencing DLT as pre-specified toxicities
RP2D will be determined by the proportion of subjects experiencing the dose-limiting toxicity (DLT) of any selected toxicity that is specified in the protocol within one-month post-injection
Time frame
1 month post-injectionSecondary outcomes
1
Change in xerostomia scores
Xerostomia will be assessed by quality of life xerostomia (XeQoL) scores. XeQoL is a 15-item questionnaire, where items 1-14 are scored as: 0=not at all; 1=a little; 2=somewhat; 3=quite a bit; 4=very much. Item 15 is scored as: 0=delighted; 1=mostly satisfied; 2=mixed: equally satisfied/dissatisfied; 3= mostly dissatisfied; 4=terrible. Lower scores indicate less impact of mouth/throat dryness on QoL, and higher scores indicate great impact on QoL.
Time frame
Baseline to 24 months2
Change in salivary function-rate of salivary production
Salivary function determined by measurement of salivary production (g/5 minutes); Unstimulated saliva production will be measured by participants allowing saliva to pool in the mouth over a 5 minute period, then gently guiding saliva into a saliva collection aid; Simulated saliva production will be measured by participants chewing inert gum base to the pace of a metronome (70 beats/minute) while expectorating saliva into a saliva collection aid for 5 minutes. Cryovials containing saliva will be weighed before and after saliva collection and the difference in weight (g) will represent the amount of saliva produced in 5 minutes for each condition.
Time frame
Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months3
Change in salivary function-saliva composition
Salivary function determined by compositional analysis of saliva sample - amylase (mU/mL). Low in disease, hypothesized to increase with intervention.
Time frame
Baseline, 1 month, 3 months, 6 months, 12 months, and 24 months4
Change in salivary function-saliva composition
Salivary function determined by compositional analysis of saliva sample - mucins (MUC5B in mU/mL) assessed using ELISA. Low in disease, hypothesized to increase with intervention.
Time frame
Baseline, 1 month, 3 months, 6 months, 12 months, and 24 monthsSponsors and contacts
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Source ClinicalTrials.gov