End Stage Renal DiseasePhase 2HONORRNCT02479451
Helping Olfaction and Nutrition On Renal Replacement
A Phase 2 study testing Theophylline in people with End Stage Renal Disease and Olfactory Disorders, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This clinical trial examines whether nasal theophylline administration can improve olfaction and nutrition in hemodialysis patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Renal Disease, Olfactory Disorders
- What is being tested?
- Theophylline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Jul 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ESRD requiring chronic outpatient hemodialysis
- Able to provide written consent
- Defects in smell identification and/or smell threshold detection as measured by "Scratch-and-sniff" University of Pennsylvania Smell Identification Test (UPSIT) and Smell Threshold Test
Who cannot join
- Prior allergic reaction to theophylline
- Patients currently treated with theophylline for clinical indication
- Pregnancy or lactation
- ESRD patients on peritoneal dialysis
- Patients hospitalized at the time of study enrollment
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
This clinical trial examines whether nasal theophylline administration can improve olfaction and nutrition in hemodialysis patients.
Read the detailed description
Malnutrition and cachexia are prevalent in end stage renal disease (ESRD) patients and are associated with increased morbidity and mortality. Food aversion is a major contributor to anorexia and malnutrition in ESRD and it also impacts the quality of life. Olfactory dysfunction has been shown to contribute to food aversion in ESRD patients. Since up to 80% of a meal's flavor is attributed to olfactory input, loss or alteration of smell leads to loss or alteration of taste in ESRD patients and at present there are no effective therapies to treat smell and/or taste disorders in ESRD patients.
In patients with other causes of olfactory dysfunction such as congenital hyposmia and traumatic brain injury, intranasal theophylline has been shown to be effective in improving olfactory defects via increasing nasal mucus levels of cAMP and cGMP, second messengers critical for optimal smell sensation. However, the efficacy of nasal theophylline to improve olfaction in ESRD patients has not been investigated and the effects of nasal theophylline treatment on the nutritional parameters are unknown in ESRD patients.
Aim: To examine the efficacy and safety of nasal theophylline treatment to improve olfaction and nutrition in ESRD patients
Hypothesis: Nasal theophylline treatment improves olfaction and nutrition in ESRD patients with olfactory defects by via increasing intracellular cAMP and cGMP levels.
A previous pilot clinical trial demonstrated that intranasal theophylline is safe and effective in improving olfactory deficits in congenital hyposmia and traumatic brain injury, however, it has not been examined in ESRD patients. The investigators will conduct a pilot single arm open-label clinical trial (n=20) of 6 weeks duration to examine the efficacy and safety of nasal theophylline in hemodialysis-dependent ESRD patients with olfactory defects. The investigators will examine whether nasal theophylline improves olfaction and nutritional status in trial participants.
- Conditions
- End Stage Renal Disease, Olfactory Disorders
- Being tested
- Theophylline
- Keywords
- End stage renal disease, Olfaction, Dialysis, Hemodialysis, Malnutrition
- Medical subject headings
- Kidney Failure, Chronic, Anosmia, Malnutrition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheophyllineDrug
The study medication will be provided by Foundation Care.
| Study group | Role | What they receive |
|---|---|---|
| Nasal theophylline | Experimental | 20 μg intranasal theophylline (theophylline methylpropyl paraben in a 0.4-mL saline solution) once daily (in the morning) into each naris for a total of 6 weeks Receives: Drug: Theophylline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Smell Identification Test Score at 6 Weeks
Smell identification test is a validated 40-item scratch and sniff smell identification test that was administered by study investigators. Scores on this test scale range between 0 (minimum) to 40 (maximum). Higher score indicates better ability for smell identification. Total scores are reported on this scale (no sub-scales). The unit is score on this scale.
Measured: Baseline and every 2 weeks for 6 weeks
Change From Baseline in Smell Threshold Test Score at 6 Weeks
This test determined the lowest concentration of an odor compound that is perceivable by study participants. Scores on this test scale range between -2 and -10.
Higher score indicates higher smell detection threshold (i.e. worse ability to smell). Total scores are reported on this scale (no sub-scales). The unit is score on this scale.
Measured: Baseline and every 2 weeks for 6 weeks
Secondary outcomes (1)
Change From Baseline in Plasma Theophylline Level at 6 Weeks
Plasma levels of theophylline were measured using fluorescence polarization technique. Minimum level will be 0 microgram/mL and maximum assay limit is 40 microgram/mL. Higher levels indicate increased systemic exposure to theophylline. Units on scale are microgram/mL.
Measured: Baseline and every 2 weeks for 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2015 (estimated)
- Study startOct 2015
- Primary completionJul 2022
- Study completionJul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Renal DiseaseStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital
- Investigators
- Sagar U Nigwekar, MD, MMSc, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02479451
- Sponsor's protocol ID
- 2015P001231
- Acronym
- HONORR
- Status last verified
- Nov 2023
- First submitted
- 18 Jun 2015
- Last updated
- 9 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.
PubMed 19359985Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg. 2012 Nov;138(11):1064-70. doi: 10.1001/2013.jamaoto.342.
PubMed 23165381
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Helping Olfaction and Nutrition On Renal Replacement
- ClinicalTrials.gov ID
- NCT02479451
- Acronym / sponsor ID
- HONORR / 2015P001231
- Conditions
- End Stage Renal Disease, Olfactory Disorders
- Keywords
- End stage renal disease, Olfaction, Dialysis, Hemodialysis, Malnutrition
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Oct 2015 (actual)
- Primary completion
- Jul 2022 (actual)
- Study completion
- Jul 2022 (actual)
- First posted
- 24 Jun 2015 (estimated)
- Results
- Posted 9 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial examines whether nasal theophylline administration can improve olfaction and nutrition in hemodialysis patients.
Detailed description
Malnutrition and cachexia are prevalent in end stage renal disease (ESRD) patients and are associated with increased morbidity and mortality. Food aversion is a major contributor to anorexia and malnutrition in ESRD and it also impacts the quality of life. Olfactory dysfunction has been shown to contribute to food aversion in ESRD patients. Since up to 80% of a meal's flavor is attributed to olfactory input, loss or alteration of smell leads to loss or alteration of taste in ESRD patients and at present there are no effective therapies to treat smell and/or taste disorders in ESRD patients.
In patients with other causes of olfactory dysfunction such as congenital hyposmia and traumatic brain injury, intranasal theophylline has been shown to be effective in improving olfactory defects via increasing nasal mucus levels of cAMP and cGMP, second messengers critical for optimal smell sensation. However, the efficacy of nasal theophylline to improve olfaction in ESRD patients has not been investigated and the effects of nasal theophylline treatment on the nutritional parameters are unknown in ESRD patients.
Aim: To examine the efficacy and safety of nasal theophylline treatment to improve olfaction and nutrition in ESRD patients
Hypothesis: Nasal theophylline treatment improves olfaction and nutrition in ESRD patients with olfactory defects by via increasing intracellular cAMP and cGMP levels.
A previous pilot clinical trial demonstrated that intranasal theophylline is safe and effective in improving olfactory deficits in congenital hyposmia and traumatic brain injury, however, it has not been examined in ESRD patients. The investigators will conduct a pilot single arm open-label clinical trial (n=20) of 6 weeks duration to examine the efficacy and safety of nasal theophylline in hemodialysis-dependent ESRD patients with olfactory defects. The investigators will examine whether nasal theophylline improves olfaction and nutritional status in trial participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nasal theophylline | Experimental | Drug: Theophylline20 μg intranasal theophylline (theophylline methylpropyl paraben in a 0.4-mL saline solution) once daily (in the morning) into each naris for a total of 6 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- ESRD requiring chronic outpatient hemodialysis
- Able to provide written consent
- Defects in smell identification and/or smell threshold detection as measured by "Scratch-and-sniff" University of Pennsylvania Smell Identification Test (UPSIT) and Smell Threshold Test
Key exclusion criteria (5 listed)
- Prior allergic reaction to theophylline
- Patients currently treated with theophylline for clinical indication
- Pregnancy or lactation
- ESRD patients on peritoneal dialysis
- Patients hospitalized at the time of study enrollment
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TheophyllineThe study medication will be provided by Foundation Care. | Drug | Nasal theophylline |
Primary outcome
Change From Baseline in Smell Identification Test Score at 6 Weeks
Time frame: Baseline and every 2 weeks for 6 weeks
Smell identification test is a validated 40-item scratch and sniff smell identification test that was administered by study investigators. Scores on this test scale range between 0 (minimum) to 40 (maximum). Higher score indicates better ability for smell identification. Total scores are reported on this scale (no sub-scales). The unit is score on this scale.
Change From Baseline in Smell Threshold Test Score at 6 Weeks
Time frame: Baseline and every 2 weeks for 6 weeks
This test determined the lowest concentration of an odor compound that is perceivable by study participants. Scores on this test scale range between -2 and -10. Higher score indicates higher smell detection threshold (i.e. worse ability to smell). Total scores are reported on this scale (no sub-scales). The unit is score on this scale.
1 secondary outcome
Change From Baseline in Plasma Theophylline Level at 6 Weeks
Time frame: Baseline and every 2 weeks for 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19359985Henkin RI, Velicu I, Schmidt L. An open-label controlled trial of theophylline for treatment of patients with hyposmia. Am J Med Sci. 2009 Jun;337(6):396-406. doi: 10.1097/MAJ.0b013e3181914a97.
- Background: PubMed 23165381Henkin RI, Schultz M, Minnick-Poppe L. Intranasal theophylline treatment of hyposmia and hypogeusia: a pilot study. Arch Otolaryngol Head Neck Surg. 2012 Nov;138(11):1064-70. doi: 10.1001/2013.jamaoto.342.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sagar U Nigwekar, MD, MMSc principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Theophylline in people with End Stage Renal Disease and Olfactory Disorders, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 9 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in Smell Identification Test Score at 6 Weeks (time frame: Baseline and every 2 weeks for 6 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02479451, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2024.