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Helping Olfaction and Nutrition On Renal Replacement (HONORR)

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ClinicalTrials.gov Identifier: NCT02479451
Recruitment Status : Recruiting
First Posted : June 24, 2015
Last Update Posted : March 21, 2018
Sponsor:
Information provided by (Responsible Party):
Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital

Brief Summary:
This clinical trial examines whether nasal theophylline administration can improve olfaction and nutrition in hemodialysis patients.

Condition or disease Intervention/treatment Phase
End Stage Renal Disease Olfactory Disorders Drug: Theophylline Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Helping Olfaction and Nutrition On Renal Replacement
Study Start Date : October 2015
Estimated Primary Completion Date : July 2019
Estimated Study Completion Date : July 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Nasal theophylline
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
Drug: Theophylline
The study medication will be provided by Foundation Care.




Primary Outcome Measures :
  1. 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 will be administered by study investigators. Score ranges between 0 and 40.

  2. Change from baseline in smell threshold test score at 6 weeks [ Time Frame: Baseline and every 2 weeks for 6 weeks ]
    This test determines lowest concentration of an odor compound that is perceivable by study participants. Score ranges between 2 and 10.


Secondary Outcome Measures :
  1. Change from baseline in serum albumin level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Serum albumin is one of the markers of nutritional status.

  2. Change from baseline in serum prealbumin level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Serum prealbumin is one of the markers of nutritional status.

  3. Change from baseline in serum triglyceride level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Serum triglyceride is one of the markers of nutritional status.

  4. Change from baseline in serum transferrin level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Serum transferrin is one of the markers of nutritional status.

  5. Change from baseline in nasal mucus cAMP level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Nasal cAMP is an important mediator of smell sensation. It will be measured using an ELISA assay.

  6. Change from baseline in salivary cAMP level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Salivary cAMP is an important mediator of smell sensation. It will be measured using an ELISA assay.

  7. Change from baseline in nasal mucus cGMP level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Nasal cGMP is an important mediator of smell sensation. It will be measured using an ELISA assay.

  8. Change from baseline in salivary cGMP level at 6 weeks [ Time Frame: Baseline and 6 weeks ]
    Salivary cGMP is an important mediator of smell sensation. It will be measured using an ELISA assay.

  9. Change from baseline in plasma theophylline level at 6 weeks [ Time Frame: Baseline and every 2 weeks for 6 weeks ]
    Plasma levels of theophylline will be measured using fluorescence polarization technique.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02479451


Contacts
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Contact: Sagar U. Nigwekar, MD, MMSc 617 726 7872 snigwekar@mgh.harvard.edu
Contact: Teodor G. Paunescu, PhD 617 726 3696 tpaunescu@mgh.harvard.edu

Locations
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United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Sagar Nigwekar, MD, MMSc    617-726-7872    snigwekar@mgh.harvard.edu   
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
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Principal Investigator: Sagar U Nigwekar, MD, MMSc Massachusetts General Hospital

Publications:
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Responsible Party: Sagar U. Nigwekar, MD, MMSc, Assistant in Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT02479451     History of Changes
Other Study ID Numbers: 2015P001231
First Posted: June 24, 2015    Key Record Dates
Last Update Posted: March 21, 2018
Last Verified: March 2018

Keywords provided by Sagar U. Nigwekar, MD, MMSc, Massachusetts General Hospital:
End stage renal disease
Olfaction
Dialysis
Hemodialysis
Malnutrition

Additional relevant MeSH terms:
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Kidney Diseases
Kidney Failure, Chronic
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Theophylline
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents
Purinergic P1 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents