Theophylline Treatment for Pseudohypoparathyroidism

NCT03029429 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IND 133103
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Pseudohypoparathyroidism is a genetic disorder with limited treatment options. Patients have early-onset obesity, short stature and increased risk of type 2 diabetes. This phase 2 clinical trial will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. The investigators hypothesize that theophylline will cause weight loss, improve glucose tolerance and slow growth plate closure in children and young adults.

Conditions

Pseudohypoparathyroidism; Albright Hereditary Osteodystrophy

Keywords

pseudohypoparathyroidism; AHO; Albright Hereditary Osteodystrophy

Outcome Measures

Primary Outcomes (1)

• Change in body mass index

  BMI will be expressed a percent of the 95th percentile

  baseline and 52 weeks

Secondary Outcomes (3)

• Change in insulinogenic index

  baseline and 52 weeks

• change in levothyroxine dose

  baseline and 52 weeks

• change in calcitriol dose

  baseline and 52 weeks

Other Outcomes (2)

• Change in body mass index z-score

  baseline and 52 weeks

• Change in BMI

  52 weeks

Study Arms (2)

Theophylline

EXPERIMENTAL

Theophylline capsules by mouth once daily or Theophylline elixir by mouth q6h (dose determined by serum drug levels)

Drug: Theophylline

Placebos

PLACEBO COMPARATOR

Theophylline capsule by mouth once daily or Theophylline elixir by mouth q6h

Drug: Placebos

Interventions

Theophylline DRUG

oral theophylline

Also known as: Theo-24, Elixophyllin

Theophylline

Placebos DRUG

oral placebo

Also known as: placebo

Placebos

Eligibility Criteria

• Age: 13 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 13 years and above
• Clinical diagnosis of PHP (per the EuroPHP network classification guidelines1): Presence of PTH resistance or ectopic classification OR brachydactyly type E plus 2 minor criteria (TSH resistance, other hormonal resistance, developmental delay, intrauterine or post-natal growth retardation, obesity/overweight, specific facial features)
• Obesity (BMI \>95th percentile for age/gender and/or ≥30 kg/m2)

You may not qualify if:

• Use of a PDE inhibitor in the past 30 days
• History of a seizure disorder unrelated to hypocalcemia
• History of a cardiac arrhythmia (not including bradycardia)
• Hepatic insufficiency including cirrhosis and acute hepatitis (AST or ALT \>3x upper limit of normal)
• Congestive heart failure
• Current cigarette use or alcohol abuse
• Pregnancy or intention to become pregnant during the next year
• Untreated hypothyroidism (defined as free thyroxine below the lower limit of normal)
• Active peptic ulcer disease
• Current use of medications known to effect theophylline levels
• History of hypersensitivity to theophylline or other medication components
• History of Major Depressive Disorder in the past 2 years, lifetime history of suicide attempt, history of any suicidal behavior in the past month, history of other sever psychiatric disorders (e.g. schizophrenia, bipolar disorder)
• PHQ-9 score is ≥15 or suicidal ideation of type 4 or 5 (C-SSR) in the past month
• Unable to comply with study procedures in the opinion of the investigator

Sponsors & Collaborators

• Harvard University: collaborator
• Vanderbilt University Medical Center: lead

Study Sites (1)

Jaclyn Tamaroff

Nashville, Tennessee, 37212, United States

Location

Related Publications (8)

• Shoemaker AH, Juppner H. Nonclassic features of pseudohypoparathyroidism type 1A. Curr Opin Endocrinol Diabetes Obes. 2017 Feb;24(1):33-38. doi: 10.1097/MED.0000000000000306.

  PMID: 27875418 BACKGROUND

• Wang L, Shoemaker AH. Eating behaviors in obese children with pseudohypoparathyroidism type 1a: a cross-sectional study. Int J Pediatr Endocrinol. 2014;2014(1):21. doi: 10.1186/1687-9856-2014-21. Epub 2014 Oct 15.

  PMID: 25337124 BACKGROUND

• Shoemaker AH, Lomenick JP, Saville BR, Wang W, Buchowski MS, Cone RD. Energy expenditure in obese children with pseudohypoparathyroidism type 1a. Int J Obes (Lond). 2013 Aug;37(8):1147-53. doi: 10.1038/ijo.2012.200. Epub 2012 Dec 11.

  PMID: 23229731 BACKGROUND

• Mano T, Uchimura K, Hayashi R, Kobahashi T, Fujiwara K, Makino M, Kakizawa H, Nagata M, Nakai A, Wada M, Nagasaka A, Itoh M. Increased urinary phosphate excretion in pseudohypoparathyroidism type II with long-term treatment with phosphodiesterase inhibitor. Horm Metab Res. 1999 Nov;31(11):602-5. doi: 10.1055/s-2007-978804.

  PMID: 10598827 BACKGROUND

• Landreth H, Malow BA, Shoemaker AH. Increased Prevalence of Sleep Apnea in Children with Pseudohypoparathyroidism Type 1a. Horm Res Paediatr. 2015;84(1):1-5. doi: 10.1159/000381452. Epub 2015 Apr 23.

  PMID: 25925491 BACKGROUND

• Perez KM, Lee EB, Kahanda S, Duis J, Reyes M, Juppner H, Shoemaker AH. Cognitive and behavioral phenotype of children with pseudohypoparathyroidism type 1A. Am J Med Genet A. 2018 Feb;176(2):283-289. doi: 10.1002/ajmg.a.38534. Epub 2017 Nov 28.

  PMID: 29193623 BACKGROUND

• Curley KL, Kahanda S, Perez KM, Malow BA, Shoemaker AH. Obstructive Sleep Apnea and Otolaryngologic Manifestations in Children with Pseudohypoparathyroidism. Horm Res Paediatr. 2018;89(3):178-183. doi: 10.1159/000486715. Epub 2018 Feb 16.

  PMID: 29455209 BACKGROUND

• Hanna P, Grybek V, Perez de Nanclares G, Tran LC, de Sanctis L, Elli F, Errea J, Francou B, Kamenicky P, Linglart L, Pereda A, Rothenbuhler A, Tessaris D, Thiele S, Usardi A, Shoemaker AH, Kottler ML, Juppner H, Mantovani G, Linglart A. Genetic and Epigenetic Defects at the GNAS Locus Lead to Distinct Patterns of Skeletal Growth but Similar Early-Onset Obesity. J Bone Miner Res. 2018 Aug;33(8):1480-1488. doi: 10.1002/jbmr.3450. Epub 2018 Jun 7.

  PMID: 29693731 BACKGROUND

Related Links

• Vanderbilt PHP Research Page

MeSH Terms

Conditions

Pseudohypoparathyroidism

Interventions

Theophylline

Condition Hierarchy (Ancestors)

Bone Diseases, Metabolic; Bone Diseases; Musculoskeletal Diseases; Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Calcium Metabolism Disorders

Intervention Hierarchy (Ancestors)

Xanthines; Alkaloids; Heterocyclic Compounds; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jaclyn Tamaroff, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Study Record Dates

• First Submitted: January 18, 2017
• First Posted: January 24, 2017
• Study Start: September 1, 2018
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)