Theophylline Treatment for Pseudohypoparathyroidism - Children 2-12 Years Old

NCT04551170 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: IND 133103 R01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Pseudohypoparathyroidism is a genetic disorder with limited treatment options, characterized by early-onset obesity, short stature and resistance to multiple hormones. This phase 2 clinical trial and open-label extension study will test the efficacy of theophylline, a phosphodiesterase inhibitor, in pseudohypoparathyroidism. We hypothesize that theophylline will cause weight loss, slow the rate of growth plate closure and decrease hormone resistance in children.

Conditions

Pseudohypoparathyroidism Type 1a; Albright Hereditary Osteodystrophy; Pseudohypoparathyroidism

Keywords

Pseudohypoparathyroidism; PHP; AHO; Albright Hereditary Osteodystrophy

Outcome Measures

Primary Outcomes (1)

• Change in body mass index

  BMI expressed as percent of the 95th percentile

  baseline and 52 weeks

Secondary Outcomes (3)

• Change in levothyroxine dose

  baseline and 52 weeks

• Change in calcitriol dose

  baseline and 52 weeks

• Change in epiphyseal closure

  baseline and 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

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Placebo DRUG

Placebo capsule or elixir

Placebo

Theophylline DRUG

oral theophylline

Also known as: Theo-24, Elixophyllin

Theophylline

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 2 to 12 years old
• Clinical diagnosis of PHP (per the EuroPHP network classification guidelines5): Presence of PTH resistance and/or ectopic ossification 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 (see protection of human subjects)
• 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
• Untreated hypothyroidism or uncontrolled PTH resistance (PTH \>2x upper limit of normal), or treatment of these disorders by medications other than calcitriol or levothyroxine (such as Cytomel or Armour thyroid)
• Unable to comply with study procedures in the opinion of the investigator

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Related Publications (7)

• 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

• 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

Study Record Dates

• First Submitted: September 9, 2020
• First Posted: September 16, 2020
• Study Start: July 13, 2020
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: April 29, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)