Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials

Sandesh C S Nagamani, George A. Diaz, William Rhead, Susan A. Berry, Cynthia Le Mons, Uta Lichter-Konecki, James Bartley, Annette Feigenbaum, Andreas Schulze, Nicola Longo, William Berquist, Renata Gallagher, Dennis Bartholomew, Cary Harding, Mark S. Korson, Shawn E. McCandless, Wendy Smith, Jerry Vockley, David Kronn, Robert ZoriStephen Cederbaum, J. Lawrence Merritt, Derek Wong, Dion F. Coakley, Bruce F. Scharschmidt, Klara Dickinson, Miguel Marino, Brendan H. Lee, Masoud Mokhtarani

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background: Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes. Methods: Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB). Results: After 3. months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p <0.0001), the number of symptoms per patient (2.5 vs. 1.1; p <0.0001), and frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p <0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose. Conclusions: The reduction in symptoms following 3. months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control.

Original languageEnglish (US)
Pages (from-to)29-34
Number of pages6
JournalMolecular Genetics and Metabolism
Volume116
Issue number1-2
DOIs
StatePublished - Sep 1 2015

Fingerprint

Inborn Urea Cycle Disorder
Pediatrics
Urea
Scavenging
Clinical Trials
Ammonia
Nitrogen
Odors
Health care
Labels
Therapeutics
Health
Plasmas
Heartburn
Patient Compliance
glycerol phenylbutyrate
Nausea
Abdominal Pain
Caregivers
Vomiting

Keywords

  • Ammonia
  • Glycerol phenylbutyrate
  • Health-related quality of life
  • Patient-reported outcomes
  • Sodium phenylbutyrate
  • Treatment-related symptoms

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials. / Nagamani, Sandesh C S; Diaz, George A.; Rhead, William; Berry, Susan A.; Le Mons, Cynthia; Lichter-Konecki, Uta; Bartley, James; Feigenbaum, Annette; Schulze, Andreas; Longo, Nicola; Berquist, William; Gallagher, Renata; Bartholomew, Dennis; Harding, Cary; Korson, Mark S.; McCandless, Shawn E.; Smith, Wendy; Vockley, Jerry; Kronn, David; Zori, Robert; Cederbaum, Stephen; Lawrence Merritt, J.; Wong, Derek; Coakley, Dion F.; Scharschmidt, Bruce F.; Dickinson, Klara; Marino, Miguel; Lee, Brendan H.; Mokhtarani, Masoud.

In: Molecular Genetics and Metabolism, Vol. 116, No. 1-2, 01.09.2015, p. 29-34.

Research output: Contribution to journalArticle

Nagamani, SCS, Diaz, GA, Rhead, W, Berry, SA, Le Mons, C, Lichter-Konecki, U, Bartley, J, Feigenbaum, A, Schulze, A, Longo, N, Berquist, W, Gallagher, R, Bartholomew, D, Harding, C, Korson, MS, McCandless, SE, Smith, W, Vockley, J, Kronn, D, Zori, R, Cederbaum, S, Lawrence Merritt, J, Wong, D, Coakley, DF, Scharschmidt, BF, Dickinson, K, Marino, M, Lee, BH & Mokhtarani, M 2015, 'Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials', Molecular Genetics and Metabolism, vol. 116, no. 1-2, pp. 29-34. https://doi.org/10.1016/j.ymgme.2015.08.002
Nagamani, Sandesh C S ; Diaz, George A. ; Rhead, William ; Berry, Susan A. ; Le Mons, Cynthia ; Lichter-Konecki, Uta ; Bartley, James ; Feigenbaum, Annette ; Schulze, Andreas ; Longo, Nicola ; Berquist, William ; Gallagher, Renata ; Bartholomew, Dennis ; Harding, Cary ; Korson, Mark S. ; McCandless, Shawn E. ; Smith, Wendy ; Vockley, Jerry ; Kronn, David ; Zori, Robert ; Cederbaum, Stephen ; Lawrence Merritt, J. ; Wong, Derek ; Coakley, Dion F. ; Scharschmidt, Bruce F. ; Dickinson, Klara ; Marino, Miguel ; Lee, Brendan H. ; Mokhtarani, Masoud. / Self-reported treatment-associated symptoms among patients with urea cycle disorders participating in glycerol phenylbutyrate clinical trials. In: Molecular Genetics and Metabolism. 2015 ; Vol. 116, No. 1-2. pp. 29-34.
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AU - Nagamani, Sandesh C S

AU - Diaz, George A.

AU - Rhead, William

AU - Berry, Susan A.

AU - Le Mons, Cynthia

AU - Lichter-Konecki, Uta

AU - Bartley, James

AU - Feigenbaum, Annette

AU - Schulze, Andreas

AU - Longo, Nicola

AU - Berquist, William

AU - Gallagher, Renata

AU - Bartholomew, Dennis

AU - Harding, Cary

AU - Korson, Mark S.

AU - McCandless, Shawn E.

AU - Smith, Wendy

AU - Vockley, Jerry

AU - Kronn, David

AU - Zori, Robert

AU - Cederbaum, Stephen

AU - Lawrence Merritt, J.

AU - Wong, Derek

AU - Coakley, Dion F.

AU - Scharschmidt, Bruce F.

AU - Dickinson, Klara

AU - Marino, Miguel

AU - Lee, Brendan H.

AU - Mokhtarani, Masoud

PY - 2015/9/1

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N2 - Background: Health care outcomes have been increasingly assessed through health-related quality of life (HRQoL) measures. While the introduction of nitrogen-scavenging medications has improved survival in patients with urea cycle disorders (UCDs), they are often associated with side effects that may affect patient compliance and outcomes. Methods: Symptoms commonly associated with nitrogen-scavenging medications were evaluated in 100 adult and pediatric participants using a non-validated UCD-specific questionnaire. Patients or their caregivers responded to a pre-defined list of symptoms known to be associated with the use of these medications. Responses were collected at baseline (while patients were receiving sodium phenylbutyrate [NaPBA]) and during treatment with glycerol phenylbutyrate (GPB). Results: After 3. months of GPB dosing, there were significant reductions in the proportion of patients with treatment-associated symptoms (69% vs. 46%; p <0.0001), the number of symptoms per patient (2.5 vs. 1.1; p <0.0001), and frequency of the more commonly reported individual symptoms such as body odor, abdominal pain, nausea, burning sensation in mouth, vomiting, and heartburn (p <0.05). The reduction in symptoms was observed in both pediatric and adult patients. The presence or absence of symptoms or change in severity did not correlate with plasma ammonia levels or NaPBA dose. Conclusions: The reduction in symptoms following 3. months of open-label GPB dosing was similar in pediatric and adult patients and may be related to chemical structure and intrinsic characteristics of the product rather than its effect on ammonia control.

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