Evidence map›Paper›PMID 26751191›Full record

ArticleThe Journal of clinical endocrinology and metabolism2016

Single-Dose Study of a Corticotropin-Releasing Factor Receptor-1 Antagonist in Women With 21-Hydroxylase Deficiency.

Adina F Turcu, Joanna L Spencer-Segal, Robert H Farber, Rosa Luo, Dimitri E Grigoriadis, Carole A Ramm, David Madrigal, Tim Muth, Christopher F O'Brien, Richard J Auchus

Open access · bronzeAbstract readClinical Trial, Phase IControlled Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Article in The Journal of clinical endocrinology and metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed, 2 pooled it
3.5field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Trial
  6. Article
  7. Review
  8. Approach to the Child and Adolescent With Adrenal Insufficiency.The Journal of clinical endocrinology and metabolism · 2025
    Review
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Review
  17. Block and Replace-a New Therapeutic Concept in Congenital Adrenal Hyperplasia?The Journal of clinical endocrinology and metabolism · 2022
    Article
  18. Article
  19. Review
  20. Adrenal insufficiency.Nature reviews. Disease primers · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Adina F TurcuDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Joanna L Spencer-SegalDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Robert H FarberDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Rosa LuoDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Dimitri E GrigoriadisDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Carole A RammDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
David MadrigalDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Tim MuthDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Christopher F O'BrienDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Richard J AuchusDivision of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine (A.F.T., J.L.S.-S., C.A.R., D.M., T.M., R.J.A.), and Department of Pharmacology (R.J.A.), University of Michigan, Ann Arbor, Michigan 48109; and Neurocrine Biosciences (R.H.F., R.L., D.E.G., C.F.O.), San Diego, California 92130.
Michigan Medicine · USNeurocrine Biosciences (United States) · US

Funding

MICHIGAN INSTITUTE FOR CLINICAL AND HEALTH RESEARCH (MICHR) (UL1): (BPCA)UL1RR024986 · NCRR · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHANLEY, THOMAS P. · 2007 to 2011
$51.2M
Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
TRAINING PROGRAM IN ENDOCRINOLOGY AND METABOLISM.T32DK007245 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RICHARD J. AUCHUS · 1986 to 2026
$7.2M
ENDOCRINE RESEARCH TRAINING PROGRAMT32DK007313 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI IMPERATO-MCGINLEY, JULIANNE L · 1986 to 2011
$1.9M
NCATS NIH HHS UL1 TR000433NCRR NIH HHS UL1 RR024986NCRR NIH HHS UL1-RR024986NIDDK NIH HHS T32 DK007245NIDDK NIH HHS T32DK007245NIDDK NIH HHS T32 DK007313
6 · The paper itself

Abstract

contextTreatment of 21-hydroxylase deficiency (21OHD) is difficult to optimize. Normalization of excessive ACTH and adrenal steroid production commonly requires supraphysiologic doses of glucocorticoids.

objectivesWe evaluated the safety and tolerability of the selective corticotropin releasing factor type 1 (CRF1) receptor antagonist NBI-77860 in women with classic 21OHD and tested the hypothesis that CRF1 receptor blockade decreases early-morning ACTH and 17α-hydroxyprogesterone (17OHP) in these patients.

participantsThe study enrolled eight classic 21OHD females, ages 18-58 years, seen at a single tertiary referral university setting.

designThis was a phase Ib, single-blind, placebo-controlled, fixed-sequence, single-dose trial. During three treatment periods separated by 3-week washout intervals, patients sequentially received placebo, NBI-77860 300 mg, and NBI-77860 600 mg at 10 pm; glucocorticoid therapy was withheld for 20 hours. We evaluated ACTH, 17OHP, androstenedione, and testosterone as well as NBI-77860 pharmacokinetics over 24 hours.

resultsDose-dependent reductions of ACTH and/or 17OHP were observed in six of eight subjects. Relative to placebo, NBI-77860 led to an ACTH and 17OHP reduction by a mean of 43% and 0.7% for the 300 mg dose, respectively, and by 41% and 27% for the 600 mg dose, respectively. Both NBI-77860 doses were well tolerated.

conclusionThe meaningful reductions in ACTH and 17OHP following NBI-77860 dosing in 21OHD patients demonstrate target engagement and proof of principle in this disorder. These promising data provide a rationale for additional investigations of CRF1 receptor antagonists added to physiologic doses of hydrocortisone and fludrocortisone acetate for the treatment of classic 21OHD.

Indexed as

17-alpha-HydroxyprogesteroneAdrenal Hyperplasia, CongenitalAdrenocorticotropic HormoneAdultAzabicyclo CompoundsCRF Receptor, Type 1Dose-Response Relationship, DrugFemaleHumansMiddle AgedOxadiazolesReceptors, Corticotropin-Releasing HormoneTime FactorsYoung Adult17-alpha-HydroxyprogesteroneAdrenocorticotropic HormoneAzabicyclo CompoundsCRF Receptor, Type 1NBI 77860OxadiazolesReceptors, Corticotropin-Releasing Hormone

Identifiers

PMID26751191
PMCPMC4803170
OpenAlexW2237847983

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.